Somatic egfr mutations. Medical search. Frequent questions

The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). (wikipedia.org)
Epidermal growth factor receptor (EGFR) is a transmembrane protein that is activated by binding of its specific ligands, including epidermal growth factor and transforming growth factor alpha (TGF-α). (wikipedia.org)
Although a number of studies have shown that patients with activating mutations in exons 18-21 of the epidermal growth factor receptor (EGFR) gene respond particularly well to gefitinib and erlotinib, a prospective, randomised study was needed to differentiate between the prognostic and predictive value of EGFR mutations. (ersjournals.com)
This review considers the current evidence linking biomarker profile to efficacy of epidermal growth factor receptor (EGFR)-targeted therapy in advanced nonsmall cell lung cancer (NSCLC) and the clinical implications of recent findings. (ersjournals.com)
The EGFR gene provides instructions for making a receptor protein called the epidermal growth factor receptor, which spans the cell membrane so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. (medlineplus.gov)
Lung cancers with EGFR gene mutations tend to respond to treatments that specifically target the overactive epidermal growth factor receptor protein that allows cancer cells to constantly grow and divide. (medlineplus.gov)
The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. (bmj.com)
Alterations in receptor tyrosine kinases (TKs), such as the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1, include overexpression, amplification or mutations. (bmj.com)
The present study evaluated the prognostic value of the epidermal growth factor receptor (EGFR) mutation status, and excision repair cross-complementation group 1 (ERCC1) and thymidylate synthase (TS) expression following intercalated tyrosine kinase inhibitor (TKI) therapy and platinum- and pemetrexed-based chemotherapies (subsequent second-line treatment) for patients with adenocarcinoma non-small-cell lung cancer (AC-NSCLC). (medsci.org)
The standard therapies for lung adenocarcinoma include epidermal growth factor receptor (EGFR) mutation targeted therapy and conventional chemotherapy, such as platinum- and pemetrexed-based chemotherapies. (medsci.org)
A growing understanding of cancer molecular complexity and the role of oncogenic drivers such as mutations in genes encoding the epidermal growth factor receptor ( EGFR ), V-Ki-Ras2 Kirsten Rat Sarcoma 2 ( KRAS ), (MET) and Anaplastic Lymphoma Kinase (ALK) genes have ushered in the era of targeted therapies. (nature.com)
Subsets of patients with non-small cell lung cancer (NSCLC) who carry somatic mutations in the epidermal growth factor receptor (EGFR) have responded remarkably well to a tyrosine kinase inhibitor (TKI), gefitinib. (nih.gov)
Mutations in epidermal growth factor receptor ( EGFR ), KRAS, and anaplastic lymphoma kinase ( ALK ) are mutually exclusive in patients with NSCLC, and the presence of one mutation in lieu of another can influence response to targeted therapy. (medscape.com)
Compound epidermal growth factor receptor ( EGFR ) mutations are less responsive to tyrosine kinase inhibitors (TKIs) than single EGFR mutations in non-small cell lung cancer (NSCLC). (biomedcentral.com)
Since epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, including gefitinib (GEF) have been reported to induce the apoptosis of several cancer cell lines, in the present study, we examined whether the cytotoxic effects of GEF are further enhanced under amino acid starvation (AAS) culture conditions. (spandidos-publications.com)
Epidermal growth factor receptor (EGFR) mutants play an important role in NSCLC progression. (jcancer.org)
In patients whose lung adenocarcinomas harbor epidermal growth factor receptor (EGFR) tyrosine kinase domain mutations, acquired resistance to the tyrosine kinase inhibitors (TKI) gefitinib (Iressa) and erlotinib (Tarceva) has been associated with a second-site EGFR mutation, which leads to substitution of methionine for threonine at position 790 (T790M). (aacrjournals.org)
Assessment of the epidermal growth factor receptor (EGFR) mutational status has become crucial in recent years in the molecular classification of patients with lung cancer. (spandidos-publications.com)
Aberrant epidermal growth factor receptor signaling and enhanced sensitivity to EGFR inhibitors in lung cancer. (vumc.org)
Epidermal growth factor receptor (EGFR) is occasionally amplified and/or mutated in non-small cell lung cancer (NSCLC) and can be coexpressed with other members of the HER receptor family to form functional heterodimers. (vumc.org)
Epidermal growth factor receptor (EGFR) has been validated as a therapeutic target in several human tumours, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (HNSCC). (biomedcentral.com)
The aim of this study was to retrospectively analyze epidermal growth factor receptor (EGFR) mutations detected in a real-world scenario using a large cohort of Brazilian patients with non-small-cell lung cancer (NSCLC). (bvsalud.org)
Some evidence indicates that the presence of BRAF mutation may render colorectal cancer resistant to epidermal growth factor (EGFR)-inhibitors, such as cetuximab and panitumumab. (medscape.com)

However, most lung adenocarcinomas either lack an identifiable driver oncogene, or harbour mutations in KRAS and are therefore still treated with conventional chemotherapy. (nature.com)
What conclusions about treatment can we draw from EGFR copy number or KRAS mutation status? (ersjournals.com)
Clinical practice in colon cancer also reflects the need for mutational testing to identify patients most likely to benefit from cetuximab: patients whose tumours lack a KRAS mutation (also called wild-type) show significantly increased overall survival (OS) (median 9.5 versus 4.8 months) with cetuximab, whereas those with KRAS mutations do not benefit from therapy 4 . (ersjournals.com)
Through genomic analysis of tumor samples, the researchers identified somatic mutations in EGFR, KRAS, and other target genes. (dana-farber.org)
Smoking increases the risk for KRAS-mutant lung cancers, while patients with lung cancer who are non-smokers more often develop EGFR-mutant lung cancer," Meyerson said. (dana-farber.org)
Genes that are commonly mutated in lung adenocarcinoma include TP53, EGFR, KRAS and NF1(3). (goldenhelix.com)
KRAS mutations are also predominantly found in adenocarcinomas and are seen in approximately 25% of cases. (medscape.com)
[ 9 ] Most importantly, patients with KRAS mutations seem to have a poorer prognosis and seem to be resistant to EGFR-TKIs, although the extent to which this might influence treatment selection remains somewhat unclear. (medscape.com)
[ 9 , 10 ] KRAS G12C accounts for approximately 50% of KRAS mutations in NSCLC, and approximately 14% of patients with NSCLC have a KRAS G12C mutation. (medscape.com)
Cancer biology is complex, so an alternative would be to perform multiple gene assays that could establish the somatic mutational profile of a tumour, and subsequently check if any of the mutations could be addressed therapeutically with agents targeting those specifically defined mutations (for example, BRAF, EGFR, KRAS etc. (hospitalhealthcare.com)
In my study, I have identified lots of somatic mutations in different cancer patients, such as EGFR T790M, EGFR , L858R, KRAS G12D, JAK2 V617F .etc. (biostars.org)
We describe here the application of high-resolution melting analysis (HRM) to screen for KRAS mutations in clinical cancer samples. (nih.gov)
In non-small cell lung cancer, KRAS mutations have been shown to identify a group of patients that do not respond to EGFR targeted therapies and the identification of these mutations is thus clinically important. (nih.gov)
We developed a high-resolution melting (HRM) assay to detect somatic mutations in exon 2, notably codons 12 and 13 of the KRAS gene using the intercalating dye SYTO 9. (nih.gov)
We tested 3 different cell lines with known KRAS mutations and then examined the sensitivity of mutation detection with the cell lines using 189 bp and 92 bp amplicons spanning codons 12 and 13. (nih.gov)
We then screened for KRAS mutations in 30 non-small cell lung cancer biopsies that had been previously sequenced for mutations in EGFR exons 18-21. (nih.gov)
Known KRAS mutations in cell lines (A549, HCT116 and RPMI8226) were readily detectable using HRM. (nih.gov)
Nine of the 30 non-small cell lung cancer biopsies had KRAS mutations detected by HRM analysis. (nih.gov)
Mutations in KRAS and EGFR were mutually exclusive. (nih.gov)
One of the most common somatic alterations in colon cancer and NSCLC is the presence of activating variants in the protooncogene KRAS. (metropolisindia.com)
Metropolis Healthcare is a leading diagnostics centre and pathology lab in India equipped with the latest state-of-the-art technologies that provides the KRAS-12/13 Mutation Analysis Test with a clear pricing structure. (metropolisindia.com)
Why take KRAS-12/13 Mutation Analysis Test? (metropolisindia.com)
KRAS mutations occur in one third of human cancers and cluster in several hotspots, with codons 12 and 13 being most commonly affected. (metropolisindia.com)
Current data suggest that the efficacy of EGFR-targeted therapies in colon cancer and NSCLC is confined to patients with tumors lacking KRAS mutations. (metropolisindia.com)
A positive result indicates the presence of an activating KRAS mutation and can be a useful marker by which patients are selected for EGFR-targeted therapy. (metropolisindia.com)

We believe that for the more common mutations the database allows clinicians to make more robust decisions concerning their treatment options for NSCLC," says Dr. Murray. (eurekalert.org)
What role should anti-EGFR antibodies play in NSCLC treatment, and in which patients? (ersjournals.com)
This review considers current evidence linking biomarker profile to efficacy of EGFR-targeted therapy in NSCLC, and clinical implications of recent findings. (ersjournals.com)
In NSCLC, activation of the EGFR/HER1 pathway results in a signalling cascade that promotes tumour growth and progression 6 . (ersjournals.com)
Tumour-associated activating mutations in EGFR can identify patients with NSCLC who are likely to have a good response to TKIs. (bmj.com)
3 The development of molecular targeted therapies aimed at these molecular alterations has generated great optimism for the treatment of cancers such as NSCLC, and drugs targeting the EGFR tyrosine kinase domain are now available. (bmj.com)
Low TS expression was predictive of improved OS of patients with negative EGFR-mutated advanced AC-NSCLC, whereas high ERCC1 expression resulted in poor OS in patients with positive EGFR-mutated advanced AC-NSCLC. (medsci.org)
TS and ERCC1 expression levels were effective prognostic factors for negative and positive EGFR-mutated AC-NSCLC, respectively. (medsci.org)
In conclusion, the present results indicate that the EGFR mutation status and TS and ERCC1 expression can be used as the predictors of OS after subsequent second-line treatments for AC-NSCLC. (medsci.org)
In summary, the lung is the primary tissue observed for somatic mutations in MET (21.58%) and the specific MET gene amplification is seen in 2-4% of previously untreated NSCLC (6). (goldenhelix.com)
In fact, the use of cfDNA for sensitizing and resistance somatic mutation detection in oncodrivers for NSCLC was integrated into the European Medicines Agency (EMA) approval. (nature.com)
We herein report a case of advanced NSCLC in a patient carrying mutated EGFR (delE746-A750) who had a relapse after dramatic improvement by gefitinib treatment. (nih.gov)
Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in the progression to metastatic disease. (medscape.com)
We retrospectively studied the next-generation sequencing (NGS) data of treatment-naïve tumors from 1025 NSCLC patients with compound EGFR mutations, which were sub-categorized into different combinations of common mutations (19-Del and EGFR exon 21 p.L858R), rare mutations, and variants of uncertain significance (VUSs). (biomedcentral.com)
Short in-frame deletions in exon 19 (19-Del) and point mutations in EGFR exon 21 p.L858R are the most common activating mutations in EGFR , accounting for approximately 90% of all EGFR mutations in NSCLC [ 5 , 6 ]. (biomedcentral.com)
Besides 19-Del and EGFR exon 21 p.L858R, extensive research has uncovered a wide array of rare EGFR activating or resistant mutations in NSCLC, including EGFR exon 18 p.G719X, EGFR exon 20 p.S768I, EGFR exon 21 p.L861Q, EGFR exon 20 p.T790M, and EGFR exon 20 insertions (20ins). (biomedcentral.com)
The aim of this study was to explore potential associations between genetic polymorphisms of HMGB1 and EGFR mutations in a cohort that included 280 patients with NSCLC, some of whom were smokers and others who never smoked. (jcancer.org)
We found that after adjusting for other covariates, NSCLC patients who smoked and who respectively had CG, CT, and TC heterozygotes of HMGB1 rs2249825, rs1045411, and rs1360485, were at lower risk of developing mutant EGFR , compared to those patients with wild-type homozygotes. (jcancer.org)
Moreover, significant inverse associations between the CG and CG + GG genotypes of HMGB1 rs2249825 and the EGFR hotspot mutation, an exon 19 in-frame deletion, were also observed among NSCLC patients. (jcancer.org)
In conclusion, our results suggested that HMGB1 variants are significantly inversely associated with EGFR mutations among NSCLC patients who smoked. (jcancer.org)
For example, EGFR T790M and EGFR , L858R have a high frequency in NSCLC patients. (biostars.org)
We show here that somatic deletions in the tyrosine kinase domain of EGFR were associated with increased EGFR gene copy number in NSCLC. (vumc.org)
Treatment with the specific EGFR tyrosine kinase inhibitors (TKI) gefitinib or erlotinib or the EGFR inhibitory antibody cetuximab induced apoptosis of HCC827, a NSCLC cell line with EGFR gene amplification and an exon 19 deletion. (vumc.org)
H1819, a NSCLC cell line that expresses high levels of EGFR, ErbB2, and ErbB3 but has wild-type EGFR, showed intermediate sensitivity to TKIs. (vumc.org)
Thus, in addition to EGFR mutations, other factors in NSCLC cells, such as high expression of ErbB family members, may constitutively activate AKT and sensitize cells to EGFR inhibitors. (vumc.org)
Monoclonal antibodies directed against the extracellular domain of EGFR and small molecule inhibitors of the tyrosine kinase domain of the receptor have been evaluated in the treatment of several solid tumours including CRC, NSCLC and HNSCC [ 3 ]. (biomedcentral.com)
In NSCLC, approximately 85% of patients who responded favourably to gefitinib or erlotinib, two FDA-approved small-molecule EGFR-tyrosine-kinase inhibitors, were shown to have somatic mutations in the EGFR gene. (biomedcentral.com)
CONCLUSION: This study examined the prevalence of EGFR mutations in Brazilian patients with NSCLC using different technologies, suggesting that the type of method used, directed or nondirected against specific mutations, influences the analysis, particularly for uncommon mutations, which will be missed by mutation-specific approaches such as cobas testing. (bvsalud.org)

Here, we delineated the possible oncogenic interactions between genes containing germline and somatic mutations in TNBC and non-TNBC and investigated whether there are differences in gene expression and mutation burden between the two types of breast cancer. (hindawi.com)
The investigation revealed signatures of differentially expressed and differentially somatic mutated genes between TNBC and non-TNBC. (hindawi.com)
Network and pathway analyses revealed functionally related genes interacting in gene regulatory networks and multiple signalling pathways enriched for germline and somatic mutations for each type of breast cancer. (hindawi.com)
The results show that integrative genomics is a powerful approach for delineating oncogenic interactions between genes containing germline and genes containing somatic mutations in TNBC and non-TNBC and establishes putative functional bridges between genetic and somatic alterations and the pathways they control in the two types of breast cancer. (hindawi.com)
Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. (nature.com)
Using the genomic and ancestry data, the researchers assessed the associations of somatic mutations in target genes and global ancestry groups within a single admixed population. (dana-farber.org)
Meyerson and colleagues then stratified patients by their self-reported smoking status and evaluated the association between global ancestry and mutations in target genes. (dana-farber.org)
qBiomarker Somatic Mutation PCR Arrays are translational research tools that allow rapid and accurate profiling of the somatic mutation status for important genes related to a biological pathway or disease. (qiagen.com)
Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers. (genome.jp)
DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. (kb.se)
These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. (kb.se)
Additionally, Dr. Costa served as a co-Investigator in the NIH Clinical Genome Resource (ClinGen) Consortium, and led the engineering and product management teams developing FDA-recognized medical software applications used by healthcare providers, researchers, and biotechnology companies to define the clinical relevance of genes and pathogenicity of mutations identified in patients. (stanford.edu)
These analyses revealed a mean exonic somatic mutation rate of 12.0 events/megabase and identified the majority of genes previously reported as significantly mutated in lung adenocarcinoma. (mit.edu)
Analysis of nucleotide context-specific mutation signatures grouped the sample set into distinct clusters that correlated with smoking history and alterations of reported lung adenocarcinoma genes. (mit.edu)
Numerous NGS-based tests are being developed by both companies and academic labs and these can test for point mutations, short insertions and deletions, copy number alterations and also genomic rearrangements in a wide range of genes known to be somatically mutated in cancer, using paraffin-embedded tissues and in clinically relevant turnaround times in a scalable manner depending on the specific needs. (hospitalhealthcare.com)
We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. (preprints.org)

DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. (nature.com)
It is now possible to detect somatic alterations from minute cfDNA concentrations (less than 0.1%), enabling the detection of alterations in low-volume plasma samples. (nature.com)
Rearranged during transfection (RET), kinase alterations, which include fusions and activating point mutation, lead to overactive RET signaling and uncontrolled cell growth. (medscape.com)
Whole-genome sequence analysis revealed frequent structural rearrangements, including in-frame exonic alterations within EGFR and SIK2 kinases. (mit.edu)
For example, if a lung cancer patient has the EGFR exon 19 deletion, the app can show the patient and clinician how common EGFR mutations are compared to other gene mutations and how often the exon 19 deletion is found compared to other alterations. (vicc.org)
We therefore investigated lung cancer cell lines for alterations in EGFR gene copy number, enhanced expression of EGFR and other HER family members, and EGFR coding sequence mutations and correlated these findings with response to treatment with the EGFR inhibitors and the kinetics of ligand-induced signaling. (vumc.org)
ctDNA was successfully detected in 97% women in whom somatic genomic alterations were identified, and CA 15-3 and circulating tumor cells were detected in 78% and 87%, respectively. (medscape.com)

TP53 mutations were significantly linked to higher overall stage (p=0.038) and lower disease-free survival (DFS) (p=0.039). (preprints.org)
TP53 and FBXW7 mutations are independent biomarkers for poor prognosis of DFS (p=0.042 and 0.030, respectively). (preprints.org)
TP53 was recurrently mutated in three cases, whereas CNBD1 and RB1 mutations were identified in two cases. (oncotarget.com)
Three GEP-NET patients with TP53 mutations demonstrated a durable response and one small intestinal grade (G) 1 NET patient with BRAF V600E mutation showed progression after pazopanib treatment. (oncotarget.com)
D and TP53 R249S Mutations. (who.int)
Germline mutation of one TP53 allele is found in patients with Li-Fraumeni syndrome who generally inherit a mutated TP53 gene from an affected parent. (medscape.com)

Interruption of EGFR signalling, either by blocking EGFR binding sites on the extracellular domain of the receptor or by inhibiting intracellular tyrosine kinase activity, can prevent the growth of EGFR-expressing tumours and improve the patient's condition[citation needed]. (wikipedia.org)
EGFR dimerization stimulates its intrinsic intracellular protein-tyrosine kinase activity. (wikipedia.org)
Additionally, the kinase domain of the EGFR can cross-phosphorylate the tyrosine residues of other receptors with which it is aggregated and thereby activate itself. (wikipedia.org)
Somatic mutations in this cell-surface molecule are known to affect treatment with the newer tyrosine kinase inhibitor class of drugs. (eurekalert.org)
We have known for some time that some EGFR mutations correlate with response to tyrosine kinase inhibitors for lung cancer patients," says Dr. Samuel Murray from Department of Molecular Pathology and Translational Oncology, Metropolitan Hospital, Athens, Greece. (eurekalert.org)
So we worked on the assumption that a comprehensive list of all somatic EGFR mutations coupled with data on the response of non-small-cell lung cancers treated with tyrosine kinase inhibitors (TKIs) would help clinicians determine whether a specific mutation was likely to correlate with clinical benefit. (eurekalert.org)
Lung adenocarcinoma is the result of somatic mutations primarily impacting receptor tyrosine kinase pathways. (goldenhelix.com)
Additionally, there is resistance to EGFR tyrosine kinase inhibitors, but studies and case reports suggest that tumors harboring MET amplifications have increased sensitivity to MET inhibitors (7). (goldenhelix.com)
Initial studies with the EGFR tyrosine kinase inhibitors (TKIs) gefitnib (Iressa) and erlotinib (Tarceva) demonstrated biologic and clinical activity in only a relatively limited subset of lung cancers. (medscape.com)
0.001), implying these tumors might select additional mutations to disrupt the regulation/function of the kinase domain. (biomedcentral.com)
Different subtypes of compound EGFR mutations displayed distinct clinical features and genetic architectures, and rare mutation-dominant compound EGFR mutations were associated with enriched kinase domain-resided VUSs and poor clinical outcomes. (biomedcentral.com)
Tumor cells from patients with acquired resistance were examined for secondary EGFR kinase domain mutations by molecular analyses. (aacrjournals.org)

In both never smokers and smokers, global Native American ancestry was associated with mutations in the EGFR gene, suggesting that the genomic differences associated with Native American ancestry are independent of smoking status. (dana-farber.org)
By combining allele-specific amplification and hydrolysis probe detection, qBiomarker Somatic Mutation real-time PCR assays have been developed which can detect as few as 1% somatic mutations in the background of wild-type genomic DNA. (qiagen.com)
Extensive genomic sequencing efforts in recent years have provided detailed profiles of the somatic gene mutations that occur in a wide range of human cancers. (atcc.org)

Genetic changes include mutations, gene silencing through epigenetics, gene amplification or deletion and whole chromosome gains or losses. (bmj.com)
Since the MET amplification is a common somatic mutation, the Golden Helix CancerKB catalog provided a premade interpretation for the MET gene summary (Figure 2). (goldenhelix.com)
EGFR amplification was absent in anal canal tumours (0/23), but could be identified in 4 of 24 tonsil tumours. (biomedcentral.com)
EGFR amplification was seen in tonsil but not in anal canal carcinomas. (biomedcentral.com)
Knowledge of the expression, amplification and mutation status of EGFR as well as downstream effectors such as K-RAS would help us to better understand the response of cancer patients to molecular targeted therapy. (biomedcentral.com)

A diagnosis of cancer is a life-changing event which is now made all the more complicated by our exploding knowledge about the genetic mutations in tumors. (vicc.org)
Several genetic mutations have been proposed but specific modes of inheritance are still unknown. (karger.com)
PURPOSE: There is a paucity of consistent data concerning genetic mutations in Brazilian patients with lung cancer. (bvsalud.org)

High-throughput genotyping and next-generation sequencing technologies have enabled discovery of genetic risk variants and acquired somatic mutations driving the disease. (hindawi.com)
However, the possible oncogenic interactions between germline genetic risk variants and somatic mutations in triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC) have not been characterized. (hindawi.com)
DoCM currently contains 1364 curated somatic variants in cancer. (lu.se)

Somatic mutations in the EGFR gene most often occur in a type of lung cancer called non-small cell lung cancer, specifically a form called adenocarcinoma. (medlineplus.gov)
The aim of the present study was to investigate the impact of tissue type and content of neoplastic cells in the specimen on the quality of EGFR mutation analysis among patients with lung adenocarcinoma. (spandidos-publications.com)

Studies of tumours at relapse have demonstrated expression of a T790M mutation in exon 20 of the EGFR TK domain in approximately 50% of cases. (bmj.com)
[ 5 ] By contrast, the exon 20 T790M mutation is associated with acquired resistance to TKI therapy. (medscape.com)
It is unclear how the presence of an acquired EGFR mutation such as T790M should influence therapeutic decisions. (medscape.com)

But there have been so many articles published on this topic that we felt that it would be virtually impossible for any given center or individual to interpret the clinical relevance of a given mutation. (eurekalert.org)
For decades, germline mutations, contained within the heritable genome, and somatic mutations, acquired de novo by breast cancer cells, have been considered as separate research endeavours, and each has unique clinical applications and implications for patient care. (hindawi.com)
The EGFR mutation status and ERCC1 and TS expression were the significant predictors of clinical outcomes. (medsci.org)
We determined the accuracy of MAPs plasma sequencing with respect to droplet digital polymerase chain reaction assays (ddPCR), and tested whether actionable mutation discovery is improved by next-generation sequencing (NGS) in a clinical setting. (nature.com)
[ 8 ] These data support estimates from clinical trial evidence that activating EGFR mutations are seen in approximately 50% of Asians and 10% of non-Asians. (medscape.com)
However, the detailed clinical characteristics and prognosis of various compound EGFR mutations remain to be elucidated. (biomedcentral.com)
found that EGFR 20ins had at least 80 different insertion patterns, and lung cancer patients with EGFR 20ins showed different clinical responses to various EGFR TKIs [ 13 ]. (biomedcentral.com)
HRM is a sensitive in-tube methodology to screen for mutations in clinical samples. (nih.gov)
V600E is the most common gene mutation for the BRAF gene and is the most common mutation tested for in clinical laboratories. (medscape.com)

[ 4 ] Further investigation demonstrated that the highest response rates to these TKIs were seen in patients with somatic mutations within the EGFR-TK domain, particularly exon 19 deletion, exon 21 L858R, and exon 18 G719X. (medscape.com)
Use of the EGFR-TKIs gefitinib, erlotinib, and afatinib is limited to patients with adenocarcinomas who have known activating EGFR mutations. (medscape.com)
Because EGFR and ALK mutations are mutually exclusive, patients with ALK rearrangements are not thought to benefit from EGFR-targeting TKIs. (medscape.com)

Our findings help better understand the oncogenesis of compound EGFR mutations and forecast prognostic outcomes of personalized treatments. (biomedcentral.com)

We found BRAF V600E (G1 NET from rectum and two G3 NETs from colon) and BRAF G593S (G2 NET from pancreas) missense mutations (9.1%) in an independent cohort of 44 GEP-NETs from the rectum ( n = 26), colon ( n = 7), pancreas ( n = 4), small intestine ( n = 3), stomach ( n = 3) and appendix ( n = 1) by Sanger sequencing. (oncotarget.com)
In conclusion, BRAF V600E mutation is likely to result in resistance to pazopanib but may be a potentianally actionable mutation in metastatic GEP-NETs patients. (oncotarget.com)
The researchers analyzed 150 plasma samples obtained from 106 patients with stage III/IV melanoma - 98 of whom were BRAF wildtype and eight of whom had confirmed V600E/K mutations - using a 77-gene CAPP-seq pan-cancer panel. (genomeweb.com)
BRAF gene mutation testing has emerged as an important tool for diagnosis, prognosis, treatment, and predicting patient outcome in response to targeted therapy for multiple cancer types. (medscape.com)
The BRAF gene mutation test result is positive (ie, a mutation is present) if V600E is found in the BRAF gene. (medscape.com)
Approximately 40-60% of cutaneous melanomas carry mutations in the BRAF gene.About 90% of these mutations are found to be V600E. (medscape.com)
It has marked antitumor effects against melanoma cell lines with the BRAF V600E mutation but not against cells with wild-type (non-mutated) BRAF . (medscape.com)
[ 2 ] Thus, establishing whether BRAF mutations exist in melanoma is now of critical therapeutic importance. (medscape.com)
BRAF mutation testing will likely be increasingly used in the management of colorectal cancer, as more evidence emerges regarding its usefulness. (medscape.com)
[ 4 , 5 ] Some indication exists that BRAF mutation testing may be used to evaluate the likelihood of having hereditary nonpolyposis colorectal carcinoma (HNPCC) or Lynch syndrome versus sporadic colorectal cancer. (medscape.com)
Preliminary tests, such as BRAF mutation testing, may be useful in determining which patients are likely to benefit from full gene sequencing. (medscape.com)
[ 6 ] Approximately 91% of sporadic colorectal cancers harbor BRAF mutation, whereas BRAF is almost never mutated in colorectal cancers that arise as a consequence of Lynch syndrome. (medscape.com)
[ 9 ] Thus, persons with colorectal cancers with the BRAF mutation may be unlikely to have HNPCC, and further testing with full gene sequencing is probably unwarranted. (medscape.com)
K-ras, which lies upstream of BRAF , is mutated in 30-50% of colorectal cancersand is predictive of unresponsiveness to EGFR-inhibitor targeted therapy. (medscape.com)

As discussed below, activity of the EGFR monoclonal antibody cetuximab seems to be independent of EGFR mutation status. (medscape.com)

Is it possible to test the effects of drugs like the EGFR inhibitors in primary cells? (atcc.org)

The coding sequences and splice junctions of exons 18, 19 and 21 in the EGFR gene were then screened for mutations by direct automated sequencing. (spandidos-publications.com)
The somatic status of the EGFR gene was investigated by PCR using primers specific for exons 18 through 21. (biomedcentral.com)

Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. (kb.se)
In general, activating EGFR mutations are more commonly observed in patients with adenocarcinomas and no prior history of smoking, as well as in females and those of Asian descent. (medscape.com)
[ 7 ] researchers identified EGFR mutations in 50.5% of surgically resected lung adenocarcinomas. (medscape.com)

HRM will enable high-throughput screening of gene mutations to allow appropriate therapeutic choices for patients and accelerate research aimed at identifying novel mutations in human cancer. (nih.gov)

Mutations, amplifications or misregulations of EGFR or family members are implicated in about 30% of all epithelial cancers. (wikipedia.org)
Common cancers including colorectal cancer, lung cancer and malignant melanoma are characterized by the accumulation of somatic mutations, some of which are known to affect a patient's response to cancer treatments. (pentabase.com)
EGFR mutations in lung most cancers: correlation with medical response to gefitinib remedy. (quantichrome.com)
Mutations that lead to EGFR overexpression (known as upregulation) or overactivity have been associated with a number of cancers, including squamous-cell carcinoma of the lung, anal cancers, glioblastoma and epithelial tumors of the head and neck. (ximbio.com)
POT1 mutation carriers had a range of benign and malignant neoplasms involving epithelial, mesenchymal, and neuronal tissues in addition to B- and T-cell lymphoma and myeloid cancers. (cdc.gov)
Niroula A, Vihinen M (2015) Harmful somatic amino acid substitutions affect key pathways in cancers.BMC Med Genomics 8:53. (lu.se)

The most common mutations are short deletions in exon 19 affecting the amino acid sequence LREA (DelE746-A750) or a point mutation in exon 21 resulting in the amino acid change L858R. (biomedcentral.com)

The online database brings together data on all the known somatic mutations (tumor derived - tumor specific) in a molecule called epithelial growth factor receptor (EGFR). (eurekalert.org)
After adjusting for a variety of factors, including self-reported smoking status and sample-specific tumor mutational burden, the researchers found that global Native American ancestry was positively correlated with mutations in the EGFR gene. (dana-farber.org)
The DNA sequence of the EGFR gene in a tumor biopsy specimen obtained from the relapse site revealed the presence of a second point mutation, resulting in a threonine-to-methionine amino acid substitution at position 790 of EGFR, which could not be detected in the tumor specimen taken before the treatment. (nih.gov)
ATM mutation was significantly associated with higher tumor stage (p=0.012) and shorter overall survival (OS) (p=0.041). (preprints.org)
Using these mutation signatures, we can identify patients with different cancer types, tumor stages or other characteristics. (biostars.org)
MATERIALS AND METHODS: This was a cross-sectional, observational, descriptive study on the basis of a database of EGFR molecular analysis from tumor samples of patients with a confirmatory histopathological diagnosis of primary lung cancer. (bvsalud.org)
Mutation levels in the plasma samples reflected the clonal hierarchy inferred from sequencing of tumor biopsies. (medscape.com)
The stem mutations, mutations that are carried in the bulk of an individual's disease, are going to be best for telling you something about tumor burden. (medscape.com)

Due to broader coverage and high sensitivity for insertions and deletions, sequencing via MAPs afforded important detection of additional actionable mutations. (nature.com)
To demonstrate suitability of the panels for high throughput screening, the EGFR panel was selected for evaluation using Corning Epic Technology, a label-free platform that uses optical biosensors for high sensitivity biochemical and cell-based assays. (atcc.org)
This indicates that EGFR and K-RAS mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in anal canal and tonsil squamous cell carcinoma. (biomedcentral.com)

Somatic EGFR mutations have been reported in lung carcinoma, and these mutant proteins act as substrates for targeted therapies. (bio-itworld.com)
With the availability of effective anti-EGFR therapies for various solid malignancies, such as non-cell small lung cancer, colorectal cancer and squamous cell carcinoma of the head and neck, the knowledge of EGFR and K-RAS status becomes clinically important. (biomedcentral.com)

We performed network and pathway analyses to discover molecular networks and signalling pathways enriched for germline and somatic mutations. (hindawi.com)
Achieving that goal requires understanding the germline somatic mutation interaction landscape and discovery of molecular markers driving each disease and distinguishing the two types of breast cancer. (hindawi.com)
qBiomarker Somatic Mutation PCR Arrays are intended for molecular biology applications. (qiagen.com)

In patients suffering from TNBC, the deregulation of various signalling pathways (Notch and Wnt/beta-catenin), EGFR protein have been confirmed. (genome.jp)

exon 18 mutations were detected in one case (1.7%), whereas exon 19 and 21 mutations were detected in 30 (51%) and 28 (47.3%) cases, respectively. (spandidos-publications.com)

The mean somatic mutation rate across the TCGA cohort was 8.87 mutations per megabase (Mb) of DNA (range: 0.5-48, median: 5.78). (nature.com)
A total of 17 POT1 mutation carriers and 21 noncarrier relatives were initially included in the study, and a validation cohort of 6 additional mutation carriers was subsequently recruited. (cdc.gov)

To view all methylation probes within or in close proximity to EGFR_ENST00000638463 please use the COSMIC Genome Browser . (sanger.ac.uk)
We addressed this problem by integrating germline mutation information from genome-wide association studies with somatic mutation information from next-generation sequencing using gene expression data as the intermediated phenotype. (hindawi.com)
The researchers next developed a local Native American ancestry risk score to evaluate the association of ancestry with EGFR mutation frequency across multiple distinct sites in the genome. (dana-farber.org)
They found that the correlation between ancestry and increased mutation frequency in the EGFR gene was stronger at the local genome level than the global genome level. (dana-farber.org)

Deficient signaling of the EGFR and other receptor tyrosine kinases in humans is associated with diseases such as Alzheimer's, while over-expression is associated with the development of a wide variety of tumors. (wikipedia.org)

To directly assess the functional effects of these mutations, site-directed mutant receptors were transiently expressed in CHO-K1 cells and cAMP accumulation stimulated by recombinant eelLH (rec-eelLH) was measured by homogeneous time-resolved fluorescence (HTRF) assays. (preprints.org)
SensiScreen® qPCR-based assays provide fast and reliable somatic mutation detection to support rapid initiation of the optimal cancer treatment. (pentabase.com)

The EGFR family: not so prototypical receptor tyrosine kinases. (medlineplus.gov)

A total of 12,244 patients are included, of whom 3,381 had somatic mutations in EGFR. (eurekalert.org)
EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. (nature.com)
Screening subjects with EGFR mutations therefore allows us to identify patients who can be successfully treated with gefitinib. (nih.gov)
Within patients harboring mutant EGFR , HMGB1 rs1360485 C (TC + CC) allele carriers were at higher risk of developing poorly differentiated cancer types (odds ratio=5.493, 95% confidence interval: 1.130~26.696, p =0.019), compared to patients with TT homozygotes. (jcancer.org)
Furthermore, we found that HMGB1 rs1360485 polymorphisms seemed to be related to susceptibility to developing poorly differentiated cancer linked to tobacco consumption in EGFR mutant patients. (jcancer.org)
We aimed to elucidate the frequency and nature of secondary EGFR mutations in patients with acquired resistance to TKI monotherapy. (aacrjournals.org)
EGFR mutations were more frequent in females and patients that had never smoked. (spandidos-publications.com)
In practice, there would only be a small number of patients who might actually carry the mutation and therefore benefit from the targeted therapy. (hospitalhealthcare.com)
Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. (preprints.org)
Approximately 97.9% (142) of patients showed somatic mutations. (preprints.org)
Stage 3 and 4 patients with ATM mutations (p=0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p=0.002). (preprints.org)
Patients with at least one mutation represented 24.2% of the total sample. (bvsalud.org)
Among the positive patients, the majority had just one mutation, but two or more simultaneous mutations were observed in 1.52% of patients. (bvsalud.org)
All others were considered uncommon mutations and were observed in 18.5% of all mutated patients and 4.0% of the total sample (2.3%-18.7% depending on the sequencing method). (bvsalud.org)
Evidence exists that vemurafenib improves overall and progression-free survival in patients with advanced melanoma with the V600E mutation. (medscape.com)

Under this is shown the amino acid sequence and the Pfam protein structures, followed by complex mutations and insertions and deletions. (sanger.ac.uk)

The distribution of the mutations among primary and metastatic tissues exhibited no significant differences in the proportions of EGFR mutations detected. (spandidos-publications.com)
Serial changes in circulating levels of subclonal private mutations correlated with different treatment responses between metastatic sites. (medscape.com)

These mutations are displayed at the amino acid level across the full length of the gene by default. (sanger.ac.uk)
This dataset consists of somatic variations leading to amino acid substitutions and that lead to loss of protein activity in tumours. (lu.se)
This dataset consists of somatic variations leading to amino acid substitutions that are annotated as pathogenic in ClinVar database . (lu.se)

A number of techniques have been employed for genotypic assessment of tumour-associated DNA to identify EGFR mutations, each of which has advantages and disadvantages. (bmj.com)

MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. (nature.com)
In addition to validating the gene copy number variations and mutations within cell lines, ATCC also tests the related gene expression by real-time PCR and related protein expression by Western blot. (atcc.org)
EGFR protein expression and EGFR gene copy number were analysed by means of immunohistochemistry and fluorescence in situ hybridisation. (biomedcentral.com)
EGFR mutations were absent from squamous cell carcinoma of the anus and tonsils, but EGFR protein expression was detected in the majority of the cases. (biomedcentral.com)

Benchmarking mutation effect prediction algorithms using functionally validated cancer-related missense mutations. (lu.se)

Mouse insertional mutagenesis experiments DO NOT support the designation of EGFR_ENST00000638463 as a cancer causing gene. (sanger.ac.uk)
In many cancer types, mutations affecting EGFR expression or activity could result in cancer. (wikipedia.org)
Breast cancer development and progression involve both germline and somatic mutations. (hindawi.com)
At least eight mutations in the EGFR gene have been associated with lung cancer. (medlineplus.gov)
Nearly all these EGFR gene mutations occur during a person's lifetime (somatic) and are present only in cancer cells. (medlineplus.gov)
Somatic EGFR gene mutations occur more frequently in Asian populations than in white populations, occurring in 30 to 40 percent of affected Asians compared to 10 to 15 percent of whites with lung cancer. (medlineplus.gov)
Most of the somatic EGFR gene mutations that are associated with lung cancer delete genetic material in a part of the gene known as exon 19 or change DNA building blocks (nucleotides) in another region called exon 21. (medlineplus.gov)
Previous work has demonstrated that EGFR-mutant lung cancer is more common among populations from East Asia compared with populations from North America or Europe, about 50 percent versus 10 percent of lung cancer cases, respectively," said Meyerson, who is also a professor of genetics and medicine at Dana-Farber Cancer Institute and Harvard Medical School and an Institute Member of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts. (dana-farber.org)
But it is not clear whether the ethnic difference in EGFR-mutant lung cancer is due to environmental or genetic factors," he added. (dana-farber.org)
However, we show in our study that EGFR-mutant lung cancer is also elevated among smokers with Native American ancestry. (dana-farber.org)
With the increasing knowledge of mutations involved in cancer, it is imperative to have a tertiary analysis pipeline that provides users with the most up to date information on somatic mutations. (goldenhelix.com)
What used to be "breast cancer" or "colon cancer" or "lung cancer" are now many different diseases defined by their genetics and specific treatments associated with these mutations. (vicc.org)
The app displays population-level information about somatic cancer mutations, relative to a single patient, in a user-friendly mobile environment. (vicc.org)
I want to identify is whether some mutations more likely to appear in specific cancer types or stages. (biostars.org)
Thus, different cancer types or stages can have different mutation signatures. (biostars.org)
Less understood are a newly recognized group of cancer-prone syndromes that are associated with mutations that lengthen telomeres. (cdc.gov)
The database of Cancer Passenger Mutations (dbCPM) for curated passenger variations that are unlikely to engage in cancer development, progression, or therapy. (lu.se)
DoCM: a database of curated mutations in cancer. (lu.se)

Further, the researchers found that Native American ancestry was predominantly associated with oncogenic mutations in the EGFR gene, but not with non-oncogenic mutations. (dana-farber.org)

In addition, we identified statistically recurrent somatic mutations in the splicing factor gene U2AF1 and truncating mutations affecting RBM10 and ARID1A. (mit.edu)

The EGFR mutation status and ERCC1 and TS expression were evaluated through direct DNA sequencing and immunohistochemical analyses, respectively. (medsci.org)

Anatomy8

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Diseases25

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Analytical, Diagnostic and Therapeutic Techniques and Equipment53

Psychiatry and Psychology1

Phenomena and Processes94

Disciplines and Occupations2

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KRAS25

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TP536

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Exon 181

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Patients15

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