Brca2 checkpoint kinase cell cycle checkpoint gene. Medical search. Frequent questions

Genetic testing for deleterious mutations in breast cancer 1, early onset gene ( BRCA1 ) and BRCA2 can provide key information to guide clinical decision making. (jci.org)
Women who are heterozygous carriers of mutations in either gene have a 60%-80% lifetime risk of breast cancer and a 10%-40% lifetime risk of ovarian cancer ( 1 ), reflecting a very high penetrance. (jci.org)
In the clinic, genetic testing for BRCA1 and BRCA2 mutations is offered to women in high-risk families and yields one of several possible results. (jci.org)
That's important, because typically in clinical trials we lump together patients with BRCA1 and BRCA2 mutations. (yale.edu)
He's currently researching whether these alleles alone cause resistance to PARP inhibitors and other cancer treatments-and therefore, these studies could impact clinical management of patients harboring BRCA2 mutations. (yale.edu)
Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. (gsea-msigdb.org)
DUSP4 alterations lead to hyperactivation of MAPK signaling in many cancers, including breast cancer, which often harbor mutations in cell cycle checkpoint genes, particularly in TP53. (biomedcentral.com)
This study identifies a novel mechanism for breast tumorigenesis implicating Dusp4 loss and p53 mutations in cellular acquisition of Dbf4 upregulation as a driver of cellular replication and cell cycle checkpoint escape. (biomedcentral.com)
We find that together with loss-of-function mutations in p53 and, to some degree, potentiated by cMyc overexpression, Dusp4 deletion aids in cell cycle checkpoint escape while simultaneously potentiating hallmarks of replicative stress, including multinucleation and Chk1 phosphorylation. (biomedcentral.com)
Mutations in this gene have been associated with Peutz-Jeghers syndrome, an autosomal dominant disorder characterized by the growth of polyps in the gastrointestinal tract, pigmented macules on the skin and mouth, and other neoplasms. (cancerindex.org)
Comprehensive genomic tumor profiling helps to detect clinically relevant mutations in cancer-associated genes of solid tumors and provides valuable information for selecting the most efficient treatment for each patient. (cegat.com)
The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)
Initiation and propagation of tumors reflect underlying genomic alterations such as mutations, polymorphisms, and copy number variations found in genes of multiple cellular pathways. (hindawi.com)
Inherited mutations in a small number of genes account for about five to ten percent of women's cancers.These inherited variations, identified in breast, ovarian, and endometrial cancer susceptibility, can be characterized in the general population by their frequency and the magnitude of their impact upon a patient (Table 1 ).Some inherited variants occur rarely in the general population, but confer large risks to the individual. (hindawi.com)
Although inherited mutations in a small number of genes account for only about five to ten percent of women's cancers, by far the BRCA1 and BRCA2 gene mutations are the most common examples of this observation (50-70% of familial breast cancers) [ 2 ]. (hindawi.com)
We recently reported that a sequence variant in the cell-cycle-checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations. (ox.ac.uk)
Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. (lookformedical.com)
Mutations in this gene predispose humans to breast and ovarian cancer. (lookformedical.com)
Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not. (lookformedical.com)
The most prominent target gene is BRCA, in which mutations were first identified in breast cancer and ovarian cancer. (biomedcentral.com)
For tumor cells with BRCA mutations, HRR loss would result in cell death. (biomedcentral.com)
Pancreatic cancer has also been reported to have a strong relationship with BRCA gene mutations, which indicates that pancreatic cancer patients may benefit from PARP inhibitors. (biomedcentral.com)
A family history of pancreatic cancer is an essential risk factor [ 20 ], and germline BRCA2 mutations comprise the highest proportion of known reasons for inherited pancreatic cancer [ 21 ]. (biomedcentral.com)
Researchers have identified several hundred mutations in the ATM gene that cause ataxia-telangiectasia. (diff.org)
disorder have mutations in both copies of the ATM gene in each cell. (diff.org)
protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (diff.org)
this protein prevents efficient repair of DNA damage, leading to the accumulation of mutations in other genes. (diff.org)
These modifications comprise point mutations, changes in the gene copy number, complete rearrangements, and epigenetic alterations [ 3 ] . (encyclopedia.pub)
PARP inhibitors (PARPis) can induce synthetic lethality in cancer cells with preexistent defects in the homologous recombination (HR) repair pathway, such as deleterious mutations of the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) suppressor genes [ 7 ] [ 8 ] . (encyclopedia.pub)
However, the reduction of BRCA expression due to the modulation of EF2 transcriptional factors, cyclin-dependent kinases changes in methylation of histones [ 12 ] , or disruption of other DDR effectors [ 13 ] can similarly impair HR repair, resulting in the same phenotype observed for BRCA mutations. (encyclopedia.pub)
Unraveling of GBM biology found mutations [ 1 ] in other genes that also result in BRCAness and confer sensitivity to PARPi treatment. (encyclopedia.pub)
ALL cancers have lots of additional changes, the so-called 'passenger' mutations, that may contribute to the cancer, but are not the main genes. (cancerquest.org)
Cell-free DNA in the supernatant of pleural effusion can be used to detect driver and resistance mutations, and can guide tyrosine kinase inhibitor treatment decisions. (cdc.gov)
A correlation was seen in patients with high grade serous ovarian cancer who inherited BRCA1 mutations, but not in those with inherited BRCA2 mutations. (shu.edu)

To date, inheritance of a mutant BRCA1 or BRCA2 gene is the best-established indicator of an increased risk of developing breast cancer. (jci.org)
Most women have a 12% chance of developing breast cancer in their lifetime, and women with mutated BRCA1 or BRCA2 genes may have as much as an 80% chance, and they are more likely to develop it at an early age. (biotopics.co.uk)

Individuals carrying a mutation in the breast cancer 1, early onset gene ( BRCA1 ) are at increased risk of breast or ovarian cancer and thus are candidates for risk reduction strategies such as oophorectomy and mastectomy. (jci.org)
Yale Cancer Center has an especially impressive armamentarium in the study of BRCA1 and BRCA2, proteins involved with DNA repair that, when mutated, can cause breast , ovarian , prostate , and pancreatic cancers. (yale.edu)
In collaboration with AstraZeneca, Jensen has focused on three BRCA2 reversion alleles, containing deletions in the BRCA2 gene that reactivate DNA repair functions, in tumor cell DNA from ovarian cancer patients who relapsed on a PARP inhibitor. (yale.edu)
Most cases of breast cancer do not 'run in families', but the well-known genes BRCA1 and BRCA2 can increase the risk of developing breast cancer (and also ovarian cancer). (biotopics.co.uk)
Examples of these genes are BRCA1 and BRCA2 in breast and ovarian cancers. (hindawi.com)
Pancreatic cancer is the third most common cancer related to early-onset gene mutation in breast cancer (BRCA, breast cancer susceptibility genes) as well as ovarian cancer. (biomedcentral.com)
Researches with the Ovarian Tumor Tissue Analyses Consortium analyzed the CD8+ (cytotoxic T-cell) content of tumors from 5,500 patients and compared them with clinical outcome. (shu.edu)
The analysis was large enough to allow for comparison by histologic subtype - endometrioid, clear cell , mucinous, and low-grade serous ovarian cancer, as well as high-grade serous ovarian cancer. (shu.edu)
Looking at the other histologic types, CD+ positivity was correlated with survival among patients with endometrioid and mucinous tumors, but not for clear cell or low grade serous ovarian cancer. (shu.edu)
However, patients with clear cell ovarian cancer respond well to immune checkpoint (anti-PD-1) therapy. (shu.edu)
The authors concluded that more information is needed before clinicians can identify which ovarian cancer patients will respond to checkpoint therapy. (shu.edu)
Survival Analyses of Patients with Ovarian Carcinoma, According to the Presence or Absence of Intratumoral T Cells. (shu.edu)
Panels A and B show Kaplan-Meier curves for the duration of progression-free survival and overall survival, respectively, according to the presence or absence of intratumoral T cells in 174 patients with stage III or IV epithelial ovarian cancer and complete, partial, or no response to therapy. (shu.edu)

The genes TP53 and CHEK2 are also associated with an increased risk of breast cancer. (biotopics.co.uk)
An example of this class of genes is a mutation in the CHEK2 gene in breast cancer. (hindawi.com)

Sequence analysis of these genes is being used to identify BRCA1/2 mutation carriers, though these efforts are hampered by the high frequency of variants of unknown clinical significance (VUSs). (jci.org)
A mutation, or (increased or abnormal) methylation, in a tumour suppressor gene may adversely affect the expression or transcription of the gene so that the amino acid sequence and hence the primary structure of its polypeptide product is altered. (biotopics.co.uk)
If a mutation occurs in the proto-oncogene, producing an oncogene , more of these proteins are produced and this leads to unregulated cell division, a slower rate of cell differentiation and increased inhibition of the normal cell death, so cells build up, causing cancer and forming a tumour. (biotopics.co.uk)
Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. (bmbreports.org)
DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. (bmbreports.org)
Despite these advances made in identifying inherited breast cancer susceptibility genes, the vast majority of breast cancers are sporadic, that is, no identifiable mutation in one of the known breast cancer susceptibility genes. (hindawi.com)
Mutation gene sequencing has shown several gene associations that may account for its carcinogenesis, revealing a promising research direction. (biomedcentral.com)

This review focuses on an up-to-date understanding of the functions of E3 ligases in cancers and debates the perspectives of cancer cells that rely on inhibition or activation of ubiquitylation of target proteins. (bmbreports.org)
Genome wide association studies, fluorescence in situ hybridization, comparative genomic hybridization, and candidate gene studies have enumerated genetic contributors to cancers in women. (hindawi.com)
A diagram showing the major cancer genes for some cancers. (cancerquest.org)
Clear cell and mucinous cancers were more likely to have no CD8+ positive cells. (shu.edu)

EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. (proteopedia.org)
regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. (proteopedia.org)
In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. (proteopedia.org)
Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. (proteopedia.org)
Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. (proteopedia.org)
Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription. (proteopedia.org)
CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair. (proteopedia.org)
In this study, we show that Tip60 is required for the early DNA damage response (DDR) to UV, including the phosphorylation of histone 2AX, c-Jun N-terminal kinases (JNKs), and ataxia telangiectasia-related substrates. (rupress.org)
Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. (arigobio.cn)
In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. (arigobio.cn)

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene. (wikipedia.org)
This gene, which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumor suppressor. (cancerindex.org)

Tumour suppression is achieved via the inhibition of cell division, induction of apoptosis (cell death) to remove altered cells, DNA damage repair, and inhibition of mechanisms that cause spread of cancer cells to other parts of the body (metastasis). (biotopics.co.uk)
In all five HPV negative and HPV positive cell lines tested, roscovitine caused inhibition of CDK1 and 2. (oncotarget.com)
2. Shen J P,Srivas R,Gross A,et al.Chemogenetic profiling identifies RAD17 as synthetically lethal with checkpoint kinase inhibition[J].Oncotarget,2015,6(34):35755-35769. (nefu.edu.cn)
Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung cancer. (cdc.gov)

According to some comprehensive genomic analyses, four major driver genes have been identified in pancreatic cancer: KRAS, CDKN2A, TP53, and SMAD4. (biomedcentral.com)

activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. (proteopedia.org)
Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. (proteopedia.org)
Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by substrate specificity determinants outside the T loop. (proteopedia.org)
Here we tested whether roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), which hereby also blocks homologous recombination (HR), can be used to enhance the radiation sensitivity of HNSCC cell lines. (oncotarget.com)
Cdk1 (cyclin-dependent kinase 1), also known as p34Cdc2 (cell division control protein kinase 2) depends on cyclin A and B and is triggered by a positive feedback loop at the end of G2 phase, which is the key event that initiates mitotic entry. (arigobio.cn)
Destruction of cyclin B during metaphase results in inactivation of Cdk1, allowing mitotic exit and cell division. (arigobio.cn)
It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)
The cyclin-dependent kinase 7 (CDK7) subunit of TFIIH regulates RNA polymerase-II-based transcription and promotes tumor progression. (biomedcentral.com)

Opportunistic testing of BRCA1, BRCA2 and mismatch repair genes improves the yield of phenotype driven hereditary cancer gene panels. (cdc.gov)

The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
This loss of brain cells causes the movement problems characteristic of ataxia-telangiectasia. (diff.org)

This gene encodes a kinase involved in spindle checkpoint function and chromosome segregation. (wikipedia.org)
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. (cancerindex.org)
HER2/neu (also called ERB B2 ) is the gene that encodes the human epidermal growth factor receptor type 2. (cancerquest.org)

A recurring problem in the clinic is that many detectable changes within the BRCA1 gene produce subtle alterations to the protein that are not easily recognized as either harmful (loss-of-function) alleles or harmless and thus inconsequential polymorphisms. (jci.org)
In this issue of the JCI , Chang, Sharan, and colleagues describe a novel system to evaluate human BRCA1 alleles for in vivo function using BACs containing human BRCA1 vectors in mouse cells and embryos (see the related article beginning on page 3160). (jci.org)

What pathways are this gene/protein implicaed in? (cancerindex.org)
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (lookformedical.com)
Cells have evolved with conserved recombination mediated genome editing pathways as a mean for repairing DSBs and restarting replication forks, thus allowing genome duplication to continue [ 8 ]. (springeropen.com)
These signaling pathways are disrupted in GBM, and despite the accumulation of DNA damage, cancerous cells will thrive, maintaining survival and pathological cell division [ 2 ] [ 4 ] . (encyclopedia.pub)
This killing process occurs only if two molecular pathways are simultaneously deficient in one cell, whereas the isolated defect is innocuous [ 6 ] . (encyclopedia.pub)

In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. (affbiotech.com)
Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. (gsea-msigdb.org)
Variations in these genes are known to significantly impact tumor pathogenesis, progression, and metastasis. (cegat.com)
In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
PARP inhibitors can trap the PARP-1 protein at a single-stranded break/DNA lesion and disrupt its catalytic cycle, ultimately leading to replication fork progression and consequent double-strand breaks. (biomedcentral.com)
8. Khoronenkova S V,Dianov G L.ATM prevents DSB formation by coordinating SSB repair and cell cycle progression[J].Proceedings of the National Academy of Sciences of the United States of America,2015,112(13):3997-4002. (nefu.edu.cn)
Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. (arigobio.cn)
Of the 30,000 or so genes that are currently thought to exist in the human genome , there is a small subset that seems to be particularly important in the prevention, development, and progression of cancer. (cancerquest.org)

Those mechanisms affect which kind of therapies might work once cancer patients relapse on PARP inhibitors, a treatment that stops PARP proteins from repairing DNA damage in cancer cells and leads to cell death. (yale.edu)
In fact they they often code for proteins that stimulate cell division, prevent cell differentiation or regulate programmed cell death (apoptosis) within normal tissues and in this way they cause a controlled turnover of functional cells within an organ. (biotopics.co.uk)
Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. (lookformedical.com)
Note that by convention gene names are italicized and the proteins they make are not. (cancerquest.org)

Both the BRCA1 and BRCA2 protein are involved in DNA repair," said Megan King , PhD , associate professor of cell biology and of molecular, cellular and development biology, and co-leader of the Radiobiology and Genome Integrity Research Program at Yale Cancer Center. (yale.edu)
The Journal of Cell Biology. (wikipedia.org)
Nature Cell Biology. (wikipedia.org)
Jiang R S,Liu M,Li C,et al.Cell cycle checkpoint protein Rad17[J].Chinese Journal of Cell Biology,2008,30(4):417-420. (nefu.edu.cn)
Cold Spring Harbor, NY -- Cold Spring Harbor Laboratory Press (CSHLP) announced the release of The Digital Cell: Cell Biology as a Data Science, available on its website in hardcover format. (cshlpress.com)

Dual specificity protein phosphatase 4 (DUSP4) is a critical negative regulator of the mitogen-activated protein kinase (MAPK) pathway and is often deleted or epigenetically silenced in tumors. (biomedcentral.com)
Following this, the differentially expressed genes (DEGs) were included in Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein‑protein interaction network and survival analyses. (cancerindex.org)
Non-homologous end joining (NHEJ), which does not depend upon sequence homology, is the key repair pathway during the G0/G1 stages of the cell cycle [ 10 ]. (springeropen.com)
In addition, eHSP90 induced ER stress in fibroblasts the phosphoinositide-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, which could become blocked from the PI3K/AKT inhibitor LY294002, and blockade of eHSP90 by 1G6-D7 markedly inhibited ER stress in the model, indicating preventive and restorative applications. (healthanddietblog.info)

Also known as BubR1, this protein is recognized for its mitotic roles in the spindle assembly checkpoint (SAC) and kinetochore-microtubule interactions that facilitate chromosome migration and alignment. (wikipedia.org)
BubR1 promotes mitotic fidelity and protects against aneuploidy by ensuring proper chromosome segregation between daughter cells. (wikipedia.org)
Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)

She already has a candidate in mind for the job: a new class of drugs called ATR kinase inhibitors. (yale.edu)
Furthermore, by leveraging genetic changes in BRCA2 directly from patients, Jensen's team hopes this "reverse translation" approach will accelerate our understanding of why BRCA2 plays such a crucial role in responding to PARP inhibitors. (yale.edu)
Poly (ADP-ribose) polymerase (PARP) inhibitors target tumor cells with a homologous recombination repair (HRR) deficiency based on the concept of synthetic lethality. (biomedcentral.com)
RNA silencing and pharmacologic inhibitors were used to evaluate the functions of CDK7/p38α/MYC/PD-L1 axis in cancer cell proliferation and antiPD-1 therapy resistance. (biomedcentral.com)

Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. (bmbreports.org)

Mesenchymal cells, immune cells, extracellular matrix (ECM) components, lymphatics, and vasculature are all present in breast cancer stroma. (biomedcentral.com)
Autoimmune Disease - An illness that causes the immune system to produce antibodies that attack healthy cells in the body by mistake. (healthywomen.org)
However, the mechanisms involved in CDK7-mediated immune evasion are unclear in non-small cell lung cancer (NSCLC). (biomedcentral.com)
Recently, immune checkpoint blockade therapies (ICBs) targeting PD-1/PD-L1 axis have exhibited significant clinical benefits. (biomedcentral.com)
Recent innovations have helped to develop prescription drugs against certain prostate cancer types, showing gene alterations that prevent the repair of damaged DNA or activate the body's anti-cancer natural immune defense. (mdpi.com)
This seems counter-intuitive - serous tumors would be considered "cold" tumors, yet, immune checkpoint blockade induces responses in these patients. (shu.edu)

4. Gohlke G,Scholz C J,Kneitz S,et al.DNA methylation mediated control of gene expression is critical for development of crown gall tumors[J].PLoS Genetics,2013,9(2):e1003267. (nefu.edu.cn)
kind of unregulated cell growth can lead to the formation of cancerous tumors. (diff.org)
The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent among patients whose tumors contained no T cells in islets. (shu.edu)
The risk is increased 1000-fold for squamous cell carcinoma, basal cell carcinoma, malignant melanoma, and fibrosarcoma and is increased 10-fold to 20-fold for other tumors. (medscape.com)

The ATR kinase communicates DNA damage to the cell and activates DNA damage checkpoints, which arrest the cell cycle to provide time for repairs. (yale.edu)
Interestingly, replication stress in Brca2-null cells activates p53 and the expression of its target genes, including senescence-inducing Ink4/Arf. (biomedcentral.com)

However, alterations to tumour suppressor genes can lead to the development of tumours. (biotopics.co.uk)
Subsequent improved understanding of the molecular alterations present in the cancer cell has enabled the development of targeted therapies for some forms of cancer. (nature.com)
DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. (bmbreports.org)
A panel of genes has been identified whose cancer genome alterations may predict whether non-metastatic prostate cancer would go on to metastasize. (mdpi.com)

CD8 depletion antibodies were used to assess the role of CD8 + T cells in combined CDK7 and PD-1 blockade. (biomedcentral.com)

A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. (lookformedical.com)
A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. (lookformedical.com)

Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). (proteopedia.org)
We found that Dusp4 loss alone is insufficient in mediating tumorigenesis, but alternatively converges with loss in Trp53 and MYC amplification to induce tumorigenesis primarily through chromosome 5 amplification, which specifically upregulates Dbf4 , a cell cycle gene that promotes cellular replication by mediating cell cycle checkpoint escape. (biomedcentral.com)
The generation of cellular models of drug resistance has been pivotal in unravelling the main effectors of resistance to traditional chemotherapy at the molecular level (i.e. intracellular drug inactivation, detoxifying systems, defects in DNA repair, apoptosis evasion, membrane transporters and cell adhesion). (nature.com)
This receptor is found in moderate levels on some normal cells and as the gene's name implies, it is involved in cellular responses to growth factors. (cancerquest.org)

Her research is focused on understanding how cells respond to DNA damage and safeguard the integrity of the genome. (mdanderson.org)
3) How does the cell protect genome stability in response to DNA replication stress? (mdanderson.org)
The analyzed gene datasets were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) database. (cancerindex.org)
In participating UK research institutions, investigators can publish open access in Genome Research, Genes & Development, RNA, and Learning & Memory without article publication charges and all staff can read the entire renowned Cold Spring Harbor journal collection. (cshlpress.com)

Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. (cancerindex.org)
PARP is a family of enzymes that comprises 17 members with different functions, such as maintenance of genomic stability, transcriptional regulation, and cell death [ 16 ] [ 17 ] . (encyclopedia.pub)
Moreover, CDK7 ablation specifically suppressed p38α/MYC-associated genes, and THZ1 inhibited MYC transcriptional activity through downregulating p38α. (biomedcentral.com)

The associations among CDK7, p38α, MYC, PD-L1, infiltrating T cells, and survival outcomes were validated in two tissue microarrays and public transcriptomic data of NSCLC. (biomedcentral.com)
The CDK7/MYC/PD-L1 signature and infiltrating T cell status collectively stratified NSCLC patients into different risk groups. (biomedcentral.com)

Furthermore, we used this assay to determine the effects of BRCA1 variants on cell cycle regulation, differentiation, and genomic stability. (jci.org)

The normal versions of genes in the first group are called proto-oncogenes. (cancerquest.org)
Numerous genes have been identified as proto-oncogenes. (cancerquest.org)
Some proto-oncogenes work to regulate cell death. (cancerquest.org)
The proto-oncogenes that have been identified so far have many different functions in the cell. (cancerquest.org)

The results were validated both by gene expression analysis and immunohistochemistry study in an independent 55 clinical samples from Fudan University Shanghai Cancer Center. (cancerindex.org)
Clinical assessment and identification of immuno-oncology markers concerning the 19-gene based risk classifier in stage IV colorectal cancer. (cdc.gov)
In 2005, another group of researchers also saw a correlation between the presence of tumor-infiltrating CD8+ T-cells and clinical outcome in a series of 117 patients . (shu.edu)

MTT colorimetric assays, colony formation assays and 5‑ethynyl‑20‑deoxyuridine incorporation assays were also conducted to evaluate ACC cell proliferation. (cancerindex.org)
Cell proliferation was recognized by CCK8 (Dojindo, Japan) following a manufacturers protocol. (healthanddietblog.info)

Given the previously reported role of DUSP4 as a p53 target, a potential cell cycle checkpoint, and in mediating senescence downstream of replication stress, we hypothesized that DUSP4 may be a critical oncogenic driver in breast cancer. (biomedcentral.com)
When damaged DNA cannot be repaired, a functional DDR machinery triggers a signaling cascade, leading to cell senescence or apoptosis. (encyclopedia.pub)

Genes and family environment in familial clustering of cancer. (who.int)

The activated version of this acts as a transcription factor regulating various gene expression events involved in the development of breast tissue in puberty and pregnancy. (biotopics.co.uk)
The top 14 hub genes were subsequently confirmed by reverse transcription‑quantitative polymerase chain reaction in ACC and adrenocortical adenoma samples. (cancerindex.org)
These events are dependent on the proper levels of transcription and translation of certain genes. (cancerquest.org)

However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. (springeropen.com)
Failure to repair DSBs can lead to unwanted consequences, such as loss of genetic information, chromosomal rearrangements and even cell death. (springeropen.com)
In culture, cells from affected individuals exhibit elevated rates of chromosomal breakage or instability, leading to chromosomal rearrangements. (medscape.com)
Table 1 provides a summary outline of the gene symbols, chromosomal locations, radiation sensitivity characteristics, immunodeficiencies, chromosome breakage characteristics, and major cancer risk for each of these disorders. (medscape.com)

An increased level of BUB1B expression was found in the CRT-recurrent cells. (wikipedia.org)
Gene expression profiling using an in vitro culture model exposed to space flight during the STS-132 mission, showed that space radiation alters the expression of DNA repair and oxidative stress response genes, indicating that melatonin counteracts the expression of these genes responsive to space radiation to promote cell survival. (bvsalud.org)
Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic (or 'omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. (gsea-msigdb.org)
Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository. (cancerindex.org)
Expression profiles analysis identifies the values of carcinogenesis and the prognostic prediction of three genes in adrenocortical carcinoma. (cancerindex.org)
The presence of intratumoral T cells independently correlated with delayed recurrence or delayed death in multivariate analysis and was associated with increased expression of interferon-γ, interleukin-2, and lymphocyte-attracting chemokines within the tumor. (shu.edu)
The study will compare gene expression differences between blistered and non-blistered skin from individuals with all subtypes of EB, as well as normal skin from non-EB subjects. (stanford.edu)

Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis. (biomedcentral.com)
Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. (gsea-msigdb.org)
One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer-associated gene BRCA1. (gsea-msigdb.org)
Using a genetically engineered mouse model, we generated mammary-specific Dusp4 -deleted primary epithelial cells to investigate the necessary conditions in which DUSP4 loss may drive breast cancer oncogenesis. (biomedcentral.com)
While this may reflect the fact that we have yet to identify the next BRCA gene, it may also reflect the polygenic nature of breast cancer susceptibility. (hindawi.com)
In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (lookformedical.com)

Rather, p53 accumulation by either knockdown of Mdm2 or addition of an Mdm2 inhibitor, Nutlin-3, before irradiation strongly attenuated the UV-induced DDR and increased cell survival. (rupress.org)
Furthermore, these three genes predicted overall survival and recurrence‑free survival in patients with ACC from the TCGA cohort. (cancerindex.org)
Identification of an eight-gene signature for survival prediction for patients with hepatocellular carcinoma based on integrated bioinformatics analysis. (cdc.gov)
Panels E and F show survival curves stratified according to the extent of residual disease for the 74 patients with a complete response to therapy, according to the presence or absence of intratumoral T cells. (shu.edu)

In the three years since, Yale's team has made significant advances in targeting the BRCA gene-dependent DNA repair axis for cancer therapy. (yale.edu)
BRCA2 DNA repair associ. (gsea-msigdb.org)
This is why only isolated DNA repair signaling is inactivated in cancer cells. (bmbreports.org)
DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. (bmbreports.org)
We list the DNA repair genes and related E3 ligases. (bmbreports.org)
Defects in the ability of cells to properly respond to and repair DNA damage result in genomic instability and underlie many forms of cancer. (mdanderson.org)
According to the transcriptome database of Halostachys caspica under the salt stress, the DNA damage repair gene DMC1 of H. caspica was cloned and named HcDMC1 . (nefu.edu.cn)
Guo C L,Wang J F,Li W J.The study of the correlation between cell radiosensitivity and DNA double strand breaks & repair[J].Chinese Journal of Radiological Medicine and Protection,2007,27(3):303-306. (nefu.edu.cn)
Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (diff.org)

This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. (bmbreports.org)

Anatomy19

Organisms4

Diseases12

Chemicals and Drugs120

Analytical, Diagnostic and Therapeutic Techniques and Equipment17

Phenomena and Processes92

Disciplines and Occupations1

Information Science3

Health Care3

Mutations34

BRCA1 or BRCA22

Ovarian13

CHEK22

Mutation7

Cancers4

Phosphorylation10

Serine2

Inhibition4

TP531

Cyclin8

Mismatch repair1

Ataxia-telangiectasia3

Encodes3

Alleles2

Pathways7

Progression8

Proteins5

Biology5

Pathway4

Mitotic3

Inhibitors4

Confer1

Immune6

Tumors4

Activates2

Alterations4

Blockade1

Tumor supp2

Cellular4

Genome4

Transcriptional3

CDK72

Regulation1

Proto-oncogenes4

Clinical3

Proliferation2

Senescence2

Familial1

Transcription3

Chromosomal4

Expression7

Breast cancer6

Survival4

Repair9

Biomarkers1