BRCA1 Protein
Genes, BRCA1
BRCA2 Protein
Genes, BRCA2
Germ-Line Mutation
Ovarian Neoplasms
Mutation
Genetic Testing
Heterozygote
Rad51 Recombinase
Genetic Predisposition to Disease
Founder Effect
Breast Neoplasms, Male
Neoplastic Syndromes, Hereditary
Neoplasm Proteins
DNA Repair
Genetic Counseling
DNA Damage
Transcription Factors
Tumor Suppressor Proteins
Pedigree
Ubiquitin-Protein Ligases
Fallopian Tube Neoplasms
Genomic Instability
Family Health
Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group. (1/929)
The natural history of hereditary and BRCA1- and BRCA2-associated epithelial ovarian cancer may differ from that of sporadic disease. The purpose of this study was to compare the clinical characteristics of BRCA1- and BRCA2-associated hereditary ovarian cancer, hereditary ovarian cancer with no identified BRCA1/2 mutation, and ovarian cancer in population-based controls. BRCA1 and BRCA2 mutation testing was carried out on index cases from 119 families with site-specific epithelial ovarian cancer or breast-ovarian cancer. We estimated overall survival in 151 patients from 57 BRCA1 and BRCA2 mutation families and compared it with that in 119 patients from 62 families in which a BRCA1/2 mutation was not identified. We compared clinical outcome and data on tumor histopathology, grade, and stage. We also compared survival in familial epithelial ovarian cancer, whether or not a mutation was identified, with that of an age-matched set of population control cases. Overall survival at 5 years was 21% (95% confidence interval, 14-28) in cases from BRCA1 mutation families, 25% (8-42) in BRCA2 mutation families, and 19% (12-26) in families with no identified mutation (P = 0.91). Survival in familial ovarian cancer cases as a whole was significantly worse than for population controls (P = 0.005). In the familial cases, we found no differences in histopathological type, grade, or stage according to mutation status. Compared to population control cases, mucinous tumors occurred less frequently in the familial cases (2 versus 12%, P<0.001), and a greater proportion of the familial cases presented with advanced disease (83% stage III/IV versus 56%; P = 0.001). We have shown that survival in familial ovarian cancer cases is worse than that in sporadic cases, whether or not a BRCA1/2 mutation was identified, perhaps reflecting a difference in biology analogous to that observed in breast cancer. (+info)Exclusion of a major role for the PTEN tumour-suppressor gene in breast carcinomas. (2/929)
PTEN is a novel tumour-suppressor gene located on chromosomal band 10q23.3. This region displays frequent loss of heterozygosity (LOH) in a variety of human neoplasms including breast carcinomas. The detection of PTEN mutations in Cowden disease and in breast carcinoma cell lines suggests that PTEN may be involved in mammary carcinogenesis. We here report a mutational analysis of tumour specimens from 103 primary breast carcinomas and constitutive DNA from 25 breast cancer families. The entire coding region of PTEN was screened by single-strand conformation polymorphism (SSCP) analysis and direct sequencing using intron-based primers. No germline mutations could be identified in the breast cancer families and only one sporadic carcinoma carried a PTEN mutation at one allele. In addition, all sporadic tumours were analysed for homozygous deletions by differential polymerase chain reaction (PCR) and for allelic loss using the microsatellite markers D10S215, D10S564 and D10S573. No homozygous deletions were detected and only 10 out of 94 informative tumours showed allelic loss in the PTEN region. These results suggest that PTEN does not play a major role in breast cancer formation. (+info)High frequency of germ-line BRCA2 mutations among Hungarian male breast cancer patients without family history. (3/929)
To determine the contribution of BRCA1 and BRCA2 mutations to the pathogenesis of male breast cancer in Hungary, the country with the highest male breast cancer mortality rates in continental Europe, a series of 18 male breast cancer patients and three patients with gynecomastia was analyzed for germ-line mutations in both BRCA1 and BRCA2. Although no germ-line BRCA1 mutation was observed, 6 of the 18 male breast cancer cases (33%) carried truncating mutations in the BRCA2 gene. Unexpectedly, none of them reported a family history for breast/ovarian cancer. Four of six truncating mutations were novel, and two mutations were recurrent. Four patients (22%) had a family history of breast/ovarian cancer in at least one first- or second-degree relative; however, no BRCA2 mutation was identified among them. No mutation was identified in either of the genes in the gynecomastias. These results provide evidence for a strong genetic component of male breast cancer in Hungary. (+info)Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2. (4/929)
PURPOSE: To determine the survival benefit and cost-effectiveness of screening Ashkenazi Jewish women for three specific BRCA1/2 gene mutations. METHODS: We used a Markov model and Monte Carlo analysis to estimate the survival benefit and cost-effectiveness of screening for three specific mutations in a population in which their prevalence is 2.5% and the associated cancer risks are 56% for breast cancer and 16% for ovarian cancer. We assumed that the sensitivity and specificity of the test were 98% and 99%, respectively, that bilateral prophylactic oophorectomy would reduce ovarian cancer risk by 45%, and that bilateral prophylactic mastectomy would reduce breast cancer risk by 90%. We used Medicare payment data for treatment costs and Surveillance, Epidemiology, and End Results data for cancer survival. RESULTS: Our model suggests that genetic screening of this population could prolong average nondiscounted survival by 38 days (95% probability interval, 22 to 57 days) for combined surgery, 33 days (95% probability interval, 18 to 43 days) for mastectomy, 11 days (95% probability interval, 4 to 25 days) for oophorectomy, and 6 days (95% probability interval, 3 to 8 days) for surveillance. The respective cost-effectiveness ratios per life-year saved, with a discount rate of 3%, are $20,717, $29,970, $72,780, and $134,273. CONCLUSION: In this Ashkenazi Jewish population, with a high prevalence of BRCA1/2 mutations, genetic screening may significantly increase average survival and, depending on costs and screening/treatment strategies, may be cost-effective by the standards of accepted cancer screening tests. According to our model, screening is cost-effective only if all women who test positive undergo prophylactic surgery. These estimates require confirmation through prospective observational studies and clinical trials. (+info)The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews. (5/929)
Three founder mutations in the cancer-associated genes BRCA1 and BRCA2 occur frequently enough among Ashkenazi Jews to warrant consideration of genetic testing outside the setting of high-risk families with multiple cases of breast or ovarian cancer. We estimated the prevalence of these founder mutations in BRCA1 and BRCA2 in the general population of Ashkenazi Jews according to age at testing, personal cancer history, and family cancer history. We compared the results of anonymous genetic testing of blood samples obtained in a survey of >5,000 Jewish participants from the Washington, DC, area with personal and family cancer histories obtained from questionnaires completed by the participants. In all subgroups defined by age and cancer history, fewer mutations were found in this community sample than in clinical series studied to date. For example, 11 (10%) of 109 Jewish women who had been given a diagnosis of breast cancer in their forties carried one of the mutations. The most important predictor of mutation status was a previous diagnosis of breast or ovarian cancer. In men and in women never given a diagnosis of cancer, family history of breast cancer before age 50 years was the strongest predictor. As interest in genetic testing for BRCA1 and BRCA2 in the Jewish community broadens, community-based estimates such as these help guide those seeking and those offering such testing. Even with accurate estimates of the likelihood of carrying a mutation and the likelihood of developing cancer if a mutation is detected, the most vexing clinical problems remain. (+info)Commercialization of BRCA1/2 testing: practitioner awareness and use of a new genetic test. (6/929)
It was our purpose to determine the characteristics of practitioners in the United States who were among the first to inquire about and use the BRCA1 and BRCA2 (BRCA1/2) genetic tests outside of a research protocol. Questionnaires were mailed to all practitioners who requested information on or ordered a BRCA1/2 test from the University of Pennsylvania (UPenn) Genetic Diagnostics Laboratory (GDL) between October 1, 1995 and January 1, 1997 (the first 15 months the test was available for clinical use). The response rate was 67% of practitioners; 54% (121/225) were genetic counselors, 39% (87/225) were physicians or lab directors. Most physicians were oncologists, pathologists, or obstetrician/gynecologists, but 20% practiced surgery or internal or general medicine. Fifty-six percent (125/225) had ordered a BRCA1/2 test for a patient; most of the rest had offered or were willing to offer testing. Of those who had offered testing, 70% had a patient decline BRCA1/2 testing when offered. Practitioners perceived that patients' fear of loss of confidentiality was a major reason for declining. Nearly 60% of practitioners reported that their patients had access to a genetic counselor, but 28% of physicians who ordered a BRCA1/2 test reported having no such access, despite the GDL's counseling requirement. The proportion of physicians reporting no access to genetic counselors for their patients increased from 22.4% in the first half of the study to 50% in the last half. Many practitioners have an interest in BRCA1/2 testing, despite policy statements that discourage its use outside of research protocols. Practitioner responses suggest that patient interest in testing seems to be tempered by knowledge of potential risks. An apparent increase in patient concern about confidentiality and inability to pay for testing could indicate growing barriers to testing. Although most practitioners reported having access to counseling facilities, perceived lack of such access among an increasing proportion of practitioners indicates that lab requirements for counseling are difficult to enforce and suggests that an increasing proportion of patients may not be getting access to counseling. (+info)Prevalence of BRCA1 and BRCA2 Jewish mutations in Spanish breast cancer patients. (7/929)
We screened the 185delAG and 5382insC (BRCA1) and the 6174delT (BRCA2) mutation in 298 Spanish women with breast cancer. Two women (one with Sephardic ancestors) presented the 185delAG mutation and the same haplotype reported in Ashkenazim with this mutation. This suggests a common origin of the 185delAG in both Sephardic and Ashkenazi populations. (+info)Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2. (8/929)
For families with a small number of cases of breast and/or ovarian cancer, limited data are available to predict the likelihood of genetic predisposition due to mutations in BRCA1 or BRCA2. In 104 families with three or more affected individuals (average 3.8) seeking counselling at family cancer clinics, mutation analysis was performed in the open reading frame of BRCA1 and BRCA2 by the protein truncation test and mutation-specific assays. In 31 of the 104 families tested, mutations were detected (30%). The majority of these mutations (25) occurred in BRCA1. Mutations were detected in 15 out of 25 families (60%) with both breast and ovarian cancer and in 16 out of 79 families (20%) with exclusively cases of breast cancer. Thus, an ovarian cancer case strongly predicted finding a mutation (P < 0.001). Within the group of small breast-cancer-only families, a bilateral breast cancer case or a unilateral breast cancer case diagnosed before age 40 independently predicted finding a BRCA1 or BRCA2 mutation (P = 0.005 and P = 0.02, respectively). Therefore, even small breast/ovarian cancer families with at least one case of ovarian cancer, bilateral breast cancer, or a case of breast cancer diagnosed before age 40, should be referred for mutation screening. (+info)There are different types of Breast Neoplasms such as:
1. Fibroadenomas: These are benign tumors that are made up of glandular and fibrous tissues. They are usually small and round, with a smooth surface, and can be moved easily under the skin.
2. Cysts: These are fluid-filled sacs that can develop in both breast tissue and milk ducts. They are usually benign and can disappear on their own or be drained surgically.
3. Ductal Carcinoma In Situ (DCIS): This is a precancerous condition where abnormal cells grow inside the milk ducts. If left untreated, it can progress to invasive breast cancer.
4. Invasive Ductal Carcinoma (IDC): This is the most common type of breast cancer and starts in the milk ducts but grows out of them and invades surrounding tissue.
5. Invasive Lobular Carcinoma (ILC): It originates in the milk-producing glands (lobules) and grows out of them, invading nearby tissue.
Breast Neoplasms can cause various symptoms such as a lump or thickening in the breast or underarm area, skin changes like redness or dimpling, change in size or shape of one or both breasts, discharge from the nipple, and changes in the texture or color of the skin.
Treatment options for Breast Neoplasms may include surgery such as lumpectomy, mastectomy, or breast-conserving surgery, radiation therapy which uses high-energy beams to kill cancer cells, chemotherapy using drugs to kill cancer cells, targeted therapy which uses drugs or other substances to identify and attack cancer cells while minimizing harm to normal cells, hormone therapy, immunotherapy, and clinical trials.
It is important to note that not all Breast Neoplasms are cancerous; some are benign (non-cancerous) tumors that do not spread or grow.
Benign ovarian neoplasms include:
1. Serous cystadenoma: A fluid-filled sac that develops on the surface of the ovary.
2. Mucinous cystadenoma: A tumor that is filled with mucin, a type of protein.
3. Endometrioid tumors: Tumors that are similar to endometrial tissue (the lining of the uterus).
4. Theca cell tumors: Tumors that develop in the supportive tissue of the ovary called theca cells.
Malignant ovarian neoplasms include:
1. Epithelial ovarian cancer (EOC): The most common type of ovarian cancer, which arises from the surface epithelium of the ovary.
2. Germ cell tumors: Tumors that develop from germ cells, which are the cells that give rise to eggs.
3. Stromal sarcomas: Tumors that develop in the supportive tissue of the ovary.
Ovarian neoplasms can cause symptoms such as pelvic pain, abnormal bleeding, and abdominal swelling. They can also be detected through pelvic examination, imaging tests such as ultrasound and CT scan, and biopsy. Treatment options for ovarian neoplasms depend on the type, stage, and location of the tumor, and may include surgery, chemotherapy, and radiation therapy.
Explanation: Genetic predisposition to disease is influenced by multiple factors, including the presence of inherited genetic mutations or variations, environmental factors, and lifestyle choices. The likelihood of developing a particular disease can be increased by inherited genetic mutations that affect the functioning of specific genes or biological pathways. For example, inherited mutations in the BRCA1 and BRCA2 genes increase the risk of developing breast and ovarian cancer.
The expression of genetic predisposition to disease can vary widely, and not all individuals with a genetic predisposition will develop the disease. Additionally, many factors can influence the likelihood of developing a particular disease, such as environmental exposures, lifestyle choices, and other health conditions.
Inheritance patterns: Genetic predisposition to disease can be inherited in an autosomal dominant, autosomal recessive, or multifactorial pattern, depending on the specific disease and the genetic mutations involved. Autosomal dominant inheritance means that a single copy of the mutated gene is enough to cause the disease, while autosomal recessive inheritance requires two copies of the mutated gene. Multifactorial inheritance involves multiple genes and environmental factors contributing to the development of the disease.
Examples of diseases with a known genetic predisposition:
1. Huntington's disease: An autosomal dominant disorder caused by an expansion of a CAG repeat in the Huntingtin gene, leading to progressive neurodegeneration and cognitive decline.
2. Cystic fibrosis: An autosomal recessive disorder caused by mutations in the CFTR gene, leading to respiratory and digestive problems.
3. BRCA1/2-related breast and ovarian cancer: An inherited increased risk of developing breast and ovarian cancer due to mutations in the BRCA1 or BRCA2 genes.
4. Sickle cell anemia: An autosomal recessive disorder caused by a point mutation in the HBB gene, leading to defective hemoglobin production and red blood cell sickling.
5. Type 1 diabetes: An autoimmune disease caused by a combination of genetic and environmental factors, including multiple genes in the HLA complex.
Understanding the genetic basis of disease can help with early detection, prevention, and treatment. For example, genetic testing can identify individuals who are at risk for certain diseases, allowing for earlier intervention and preventive measures. Additionally, understanding the genetic basis of a disease can inform the development of targeted therapies and personalized medicine."
Causes:
* Genetic mutations
* Hormonal imbalance
* Use of certain medications
* Alcohol consumption
* Obesity
Symptoms:
* Swelling or lumps in the breast tissue
* Pain or tenderness in the breasts
* Nipple discharge
* Skin dimpling or puckering
Diagnosis:
* Physical examination
* Mammography (breast X-ray)
* Ultrasound imaging
* Biopsy (removing a small sample of tissue for examination under a microscope)
Treatment depends on the type and stage of the cancer, but may include:
* Surgery to remove the tumor and surrounding tissue
* Radiation therapy (using high-energy X-rays to kill cancer cells)
* Chemotherapy (using drugs to kill cancer cells)
Prognosis is generally good if the cancer is detected early, but it can be challenging to diagnose due to the rarity of breast cancer in men and the similarity of symptoms to other conditions.
The hallmark of HNS is the presence of multiple types of cancer, often at an early age and in multiple organs. The most common types of cancer associated with HNS are breast, ovarian, colon, stomach, pancreatic, brain, and skin cancers.
There are several different types of HNS, each caused by a mutation in a specific gene. These include:
1. Familial Adenomatous Polyposis (FAP): This is the most common type of HNS and is caused by a mutation in the APC gene. It is characterized by hundreds or thousands of adenomatous polyps (small growths) in the colon, which can become malignant over time.
2. Turcot Syndrome: This rare disorder is caused by a mutation in the APC gene and is characterized by the development of numerous polyps in the colon, as well as other physical features such as short stature, intellectual disability, and facial dysmorphism.
3. Hereditary Diffuse Gastric Cancer (HDGC): This syndrome is caused by a mutation in the CDH1 gene and is characterized by the development of diffuse gastric cancer, which is a type of stomach cancer that spreads throughout the stomach.
4. Peutz-Jeghers Syndrome (PJS): This rare disorder is caused by a mutation in the STK11 gene and is characterized by the development of polyps in the gastrointestinal tract, as well as other physical features such as pigmented macules on the skin and mucous membranes.
5. Li-Fraumeni Syndrome (LFS): This rare disorder is caused by a mutation in the TP53 gene and is characterized by an increased risk of developing several types of cancer, including breast, ovarian, and soft tissue sarcomas.
There are several other rare genetic disorders that can increase the risk of developing gastric cancer, including:
1. Hereditary Gastric Precancerous Condition (HGPC): This rare disorder is caused by a mutation in the E-cadherin gene and is characterized by the development of precancerous lesions in the stomach.
2. Familial Adenomatous Polyposis (FAP): This rare disorder is caused by a mutation in the APC gene and is characterized by the development of hundreds or thousands of colon polyps, as well as an increased risk of developing gastric cancer.
3. Turcot Syndrome: This rare disorder is caused by a mutation in the APC gene and is characterized by the development of colon polyps, as well as other physical features such as intellectual disability and facial dysmorphism.
4. MEN1 Syndrome: This rare disorder is caused by a mutation in the MEN1 gene and is characterized by an increased risk of developing multiple endocrine neoplasia, which can include gastric cancer.
5. Cowden Syndrome: This rare disorder is caused by a mutation in the PTEN gene and is characterized by an increased risk of developing various types of cancer, including gastric cancer.
6. Li-Fraumeni Syndrome: This rare disorder is caused by a mutation in the TP53 gene and is characterized by an increased risk of developing various types of cancer, including gastric cancer.
It's important to note that not all individuals with these genetic disorders will develop gastric cancer, and many other factors can contribute to the development of this disease. If you have a family history of gastric cancer or one of these rare genetic disorders, it's important to discuss your risk with a qualified healthcare professional and follow any recommended screening or prevention strategies.
Benign fallopian tube neoplasms include:
* Serous cystadenomas: These are fluid-filled sacs that grow on the lining of the fallopian tube. They are usually small and do not spread to other parts of the body.
* Mucinous cystadenomas: These are similar to serous cystadenomas, but they contain a thick, mucous-like fluid.
* Adenomas: These are small, glandular tumors that grow on the lining of the fallopian tube. They are usually benign but can sometimes become cancerous over time.
Malignant fallopian tube neoplasms include:
* Fallopian tube carcinoma: This is a rare form of cancer that originates in the fallopian tube. It can be either serous or endometrioid type, depending on the type of cells involved.
* Endometrial adenocarcinoma: This is a type of cancer that originates in the lining of the uterus (endometrium) and can also involve the fallopian tubes.
The symptoms of fallopian tube neoplasms can vary depending on their size, location, and type. Some common symptoms include:
* Abnormal vaginal bleeding
* Pelvic pain or discomfort
* Abdominal pain or swelling
* Difficulty urinating or defecating
* Weakness or fatigue
The diagnosis of fallopian tube neoplasms is based on a combination of imaging studies, such as ultrasound and computed tomography (CT) scans, and tissue sampling, such as biopsy or surgical removal of the tumor. Treatment options for fallopian tube neoplasms depend on the type, size, and location of the tumor, as well as the patient's age, overall health, and fertility status.
Treatment options for fallopian tube neoplasms can include:
* Surgical removal of the tumor: This is the most common treatment for fallopian tube neoplasms, and it involves removing the affected fallopian tube and any other affected tissues.
* Chemotherapy: This is a treatment that uses drugs to kill cancer cells, and it may be used in combination with surgery or as a standalone treatment for more advanced cancers.
* Radiation therapy: This is a treatment that uses high-energy rays to kill cancer cells, and it may be used in combination with surgery or chemotherapy.
* Hysterectomy: This is a surgical removal of the uterus, and it may be recommended for more advanced cancers that have spread beyond the fallopian tubes.
* Conservative management: In some cases, small, non-invasive tumors may be monitored with regular check-ups and imaging studies rather than undergoing immediate treatment.
The prognosis for fallopian tube neoplasms depends on several factors, including the type and stage of the cancer, the patient's age and overall health, and the effectiveness of the treatment. In general, the prognosis is good for women with early-stage tumors that are treated successfully, but the prognosis is poorer for women with more advanced cancers.
There are several types of genomic instability, including:
1. Chromosomal instability (CIN): This refers to changes in the number or structure of chromosomes, such as aneuploidy (having an abnormal number of chromosomes) or translocations (the movement of genetic material between chromosomes).
2. Point mutations: These are changes in a single base pair in the DNA sequence.
3. Insertions and deletions: These are changes in the number of base pairs in the DNA sequence, resulting in the insertion or deletion of one or more base pairs.
4. Genomic rearrangements: These are changes in the structure of the genome, such as chromosomal breaks and reunions, or the movement of genetic material between chromosomes.
Genomic instability can arise from a variety of sources, including environmental factors, errors during DNA replication and repair, and genetic mutations. It is often associated with cancer, as cancer cells have high levels of genomic instability, which can lead to the development of resistance to chemotherapy and radiation therapy.
Research into genomic instability has led to a greater understanding of the mechanisms underlying cancer and other diseases, and has also spurred the development of new therapeutic strategies, such as targeted therapies and immunotherapies.
In summary, genomic instability is a key feature of cancer cells and is associated with various diseases, including cancer, neurodegenerative disorders, and aging. It can arise from a variety of sources and is the subject of ongoing research in the field of molecular biology.
BRCA2
BCCIP
RAD51
Michael Stratton
Institute of Cancer Research
BRCA1
Alan Ashworth
DMC1 (gene)
FANCG
PCID2
PALB2
HMG20B
KIF4A
PARP inhibitor
Bing Xia
Ashok Venkitaraman
DNA repair and recombination protein RAD54-like
SNAI2
Double-strand break repair model
Replication protein A1
Basal-like carcinoma
Abcam
DHX32
SHFM1
B. J. Rao
CREB-binding protein
Kum Kum Khanna
Cancer biomarker
Leishmania infantum
Fanconi anemia
Predictive medicine
Prostate cancer
DNA damage theory of aging
Cancer
Keratolytic winter erythema
Breast cancer classification
RAD51L3
DNA repair
ZMYND11
Cell cycle checkpoint
Biochip
Chromosome 13
DNA mismatch repair
FLNA
Genetic heterogeneity
List of OMIM disorder codes
Gynecologic cancer disparities in the United States
FANCA
Stephen Kowalczykowski
FANCB
High Resolution Melt
Aurora kinase B
High-grade serous carcinoma
Causes of cancer
Protein May Explain Chemo Resistance in Patients With BRCA2 Mutations | ONS Voice
BRCA2 gene: MedlinePlus Genetics
Category:Breast cancer - Wikimedia Commons
How breast cancers resist chemotherapy | National Institutes of Health (NIH)
Comprehensive Analysis of the Expression and Prognostic Value of LMAN2 in HER2+ Breast Cancer
Publication Detail
The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a...
Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open...
ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB |...
The Bachelor's Lesley Murphy Posts Pics After Her Preventive Double Mastectomy | SELF
Biomarkers Search
MeSH Browser
Reactome | BRCA2 E2663V [cytosol]
PCAT1
- Early...
Protein Structure Section 1 - Biochemistry Questions and Answers Discussion Page For Q.2
MeSH Browser
DeCS
Search | VHL CLAP/WR-PAHO/WHO
Screening for Germ-Line Rearrangements and Regulatory Mutations in BRCA1 Led to the Identification of Four New Deletions1 |...
Appendix C
Med-Chemist: October 2014
MSK Data Catalog
Top 7 Best Superfoods for a Balanced Diet - Androidizer
Classification-Index
Malignant Ovarian Tumor Imaging: Practice Essentials, Computed Tomography, Magnetic Resonance Imaging
Research Festival | Intramural Research Program | National Institutes of Health
Mutations21
- BRCA2 mutations disrupt these repair functions, increasing patients' risk for breast, ovarian, prostate, and pancreatic cancer as well as melanoma. (ons.org)
- Mutations in the BRCA2 gene are associated with an increased risk of breast cancer in both men and women, as well as several other types of cancer. (medlineplus.gov)
- Most BRCA2 gene mutations lead to the production of an abnormally small, nonfunctional version of the BRCA2 protein from one copy of the gene in each cell. (medlineplus.gov)
- As a result, less of this protein is available to help repair damaged DNA or fix mutations that occur in other genes. (medlineplus.gov)
- Many of the same BRCA2 gene mutations that increase the risk of breast cancer (described above) also increase the risk of ovarian cancer. (medlineplus.gov)
- Women with BRCA2 gene mutations have an approximately 12 to 25 percent chance of developing ovarian cancer in their lifetimes, as compared with 1.6 percent in the general population. (medlineplus.gov)
- Inherited BRCA2 gene mutations have been found to increase the risk of prostate cancer. (medlineplus.gov)
- BRCA2 gene mutations likely reduce the BRCA2 protein's ability to repair DNA, allowing potentially damaging mutations to persist in various other genes. (medlineplus.gov)
- These mutations impair the ability of the BRCA2 protein to help repair damaged DNA. (medlineplus.gov)
- It is not clear why different individuals with BRCA2 mutations develop cancers in different organs. (medlineplus.gov)
- Pre- and postmenopausal women are considered to have a high risk of ovarian cancer if they have a personal or family history of ovarian cancer, have or are suspected to have BRCA1 or BRCA2 genetic mutations, or have an elevated CA-125 level (antigen 125-a protein elevated in cancer tumor cells) as measured by a blood test. (medscape.com)
- Mutations in breast cancer susceptible genes, BRCA1 and BRCA2 are the genetic factors conferring highest risk to develop breast cancer. (nih.gov)
- Interestingly, while inactivation of both alleles of BRCA1 or BRCA2 genes is necessary for tumor development, their loss in normal cells affects cell viability, indicating that cells lacking BRCA1 or 2 are able to survive and predisposed to tumorigenesis due to mutations in other genes such as those involved in cell cycle regulation or DNA damage response. (nih.gov)
- BRCA1 and BRCA2 are sometimes called tumour suppressors because when they have certain changes, called harmful or pathogenic mutations, cancer can develop. (oncologica.com)
- DNA mutations in a gene can change what protein is made. (oncologica.com)
- Specific inherited mutations in BRCA1 and BRCA2 increase the risk of female breast and ovarian cancers, and they have been associated with increased risks of several additional types of cancer. (pvhomed.com)
- Together, BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers and about 5 to 10 percent of all breast cancers. (pvhomed.com)
- In addition, mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers overall. (pvhomed.com)
- Breast cancers associated with BRCA1 and BRCA2 mutations tend to develop at younger ages than sporadic breast cancers. (pvhomed.com)
- The effects of mutations in BRCA1 and BRCA2 are seen even when a person's second copy of the gene is normal…About 12 percent of women in the general population will develop breast cancer sometime during their lives. (pvhomed.com)
- Heterozygous carriers of mutations in the BRCA2 gene have a high risk of developing breast and other cancers. (kent.ac.uk)
BRCA1 Protein1
- In the nucleus of many types of normal cells, the BRCA1 protein interacts with RAD51 during repair of DNA double-strand breaks. (indiabix.com)
Ovarian2
- For example, 25% of patients with BRCA2 ovarian cancer will become resistant to cisplatin within six months. (ons.org)
- Autosomal dominant HEREDITARY CANCER SYNDROME in which a mutation most often in either BRCA1 or BRCA2 is associated with a significantly increased risk for breast and ovarian cancers. (bvsalud.org)
Cancers4
- Researchers have discovered a protein that may lead to a new way to prevent resistance and improve outcomes for patients whose cancers have a BRCA2 mutation. (ons.org)
- Researchers discovered an unexpected way that breast cancers cells with mutant BRCA1 or BRCA2 genes acquire drug resistance and evade chemotherapies. (nih.gov)
- An analysis of clinical information showed that expression of PTIP correlated with how patients with BRCA1- and BRCA2- mutant cancers responded to treatment with DNA-damaging agents. (nih.gov)
- Heterozygous mutation of BRCA2 is associated with an increased risk of developing cancers of the breast, ovaries, pancreas, and other sites, thus BRCA2 acts as a classic tumor suppressor gene. (nih.gov)
Brca2
- 13. New advances in the DNA damage response network of Fanconi anemia and BRCA proteins. (nih.gov)
- Although BRCA proteins are known to maintain genomic stability mainly by homologous recombination-mediated DNA damage repair, detailed mechanisms of how BRCA loss induces tumorigenesis remain unclear. (nih.gov)
Tumor suppressor6
- The BRCA2 gene provides instructions for making a protein that acts as a tumor suppressor. (medlineplus.gov)
- Tumor suppressor proteins help prevent cells from growing and dividing too rapidly or in an uncontrolled way. (medlineplus.gov)
- Understanding BRCA2 Function as a Tumor Suppressor Based on Domain-Specific Activities in DNA Damage Responses. (nih.gov)
- However, understanding BRCA2 function as a tumor suppressor is severely limited by the fact that ~70% of the encoded protein has not been tested or assigned a function in the cellular DNA damage response. (nih.gov)
- This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. (nih.gov)
- The National Cancer Institute explains what the BRCA1 and BRCA2 genes are and what they mean, "BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. (pvhomed.com)
Mutation carriers2
- In part A, cohorts of three to six patients, enriched for BRCA1 and BRCA2 mutation carriers, received niraparib daily at ten escalating doses from 30 mg to 400 mg in a 21-day cycle to establish the maximum tolerated dose. (nih.gov)
- Uptake of Preimplantation Genetic Diagnosis in Female BRCA1 and BRCA2 Mutation Carriers. (cdc.gov)
Role in maintaining t2
- By helping to repair DNA, the BRCA2 protein plays a critical role in maintaining the stability of a cell's genetic information. (medlineplus.gov)
- By influencing DNA damage repair, these three proteins play a role in maintaining the stability of the human genome. (indiabix.com)
Genetic1
- These proteins help repair damaged DNA and, therefore, play a role in ensuring the stability of the cell's genetic material. (pvhomed.com)
Replication forks3
- The researchers identified several proteins that actively promote destabilization of replication forks. (nih.gov)
- Their absence protected the DNA at replication forks and reversed the drug sensitivity of BRCA1- and BRCA2- mutant cells. (nih.gov)
- BRCA2 is an essential genome stability gene that has various functions in cells, including roles in homologous recombination, G2 checkpoint control, protection of stalled replication forks, and promotion of cellular resistance to numerous types of DNA damage. (nih.gov)
Tend to develop1
- People who inherited a BRCA1 and BRCA2 mutation tend to develop cancer at younger ages. (oncologica.com)
Several proteins1
- Using a technique that allowed Escherichia coli to produce several proteins at once, the scientists expressed and reconstituted the TSEN protein complex, which was able to cleave tRNA. (nih.gov)
Genomic2
- Thus, lack of BRCA1 and BRCA2 increases genomic instability and enhances sensitivity to DNA-damaging drugs. (nih.gov)
- Because BRCA2 functions in DNA repair via homologous recombination, this leads to genomic instability. (kent.ac.uk)
Interacts2
- In the nucleus of many types of normal cells, the BRCA2 protein interacts with several other proteins to mend breaks in DNA. (medlineplus.gov)
- The BRCA2 protein, which has a function similar to that of BRCA1, also interacts with the RAD51 protein. (indiabix.com)
Downstream2
- Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. (nih.gov)
- The latter part shows the effect of the single agents and drug combinations on HSP90 client proteins and downstream effectors. (forbetterscience.com)
Repair10
- RADX is a DNA-binding protein that helps repair and ensure accuracy of DNA copies during cell division. (ons.org)
- BRCA1 and BRCA2 are human proteins that help to repair damaged DNA. (nih.gov)
- When either of these genes is mutated, or altered, the resulting abnormal proteins may be unable to properly repair DNA. (nih.gov)
- The reduced ability to repair DNA makes cancer cells with a BRCA1 or BRCA2 mutation sensitive to treatment with DNA-damaging drugs. (nih.gov)
- Certain proteins are recruited to stalled forks to stabilize, repair, and restart the replication fork. (nih.gov)
- BRCA1 and BRCA2 genes create tumor-suppressing proteins and help repair damaged DNA. (self.com)
- The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (nih.gov)
- In normal circumstances, these genes help in producing proteins which repair DNA damage. (saintfrancishosp.com)
- BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are genes that produce proteins to repair damaged DNA. (oncologica.com)
- BRCA1, BRCA2, and p53 are all DNA repair genes. (oncologica.com)
FANCB1
- FAAP95 replaces BRCA2 as the true FANCB protein. (nih.gov)
Genome1
- Thus in certain cell types, genome instability might be driven directly by heterozygosity for BRCA2 mutation. (kent.ac.uk)
Pathway2
Tumour1
- In these individuals, BRCA2 appears to act as a tumour suppressor gene, in that loss of the wild type allele is frequently observed within tumours, leading to loss of BRCA2 function. (kent.ac.uk)
Person's1
- A harmful BRCA1 or BRCA2 mutation can be inherited from a person's mother or father. (pvhomed.com)
Genetics1
- BRCA1 and BRCA2 - update and implications on the genetics of breast cancer: a clinical perspective. (medlineplus.gov)
Predominantly1
- Remarkably, even the specific role(s) of many known domains in BRCA2 are not well characterized, predominantly because stable expression of the very large BRCA2 protein in cells, for experimental purposes, is challenging. (nih.gov)
Interaction1
- Two Missense Variants Detected in Breast Cancer Probands Preventing BRCA2-PALB2 Protein Interaction. (cdc.gov)
Cells7
- However, the cells can acquire a secondary mutation that restores normal BRCA2 function and causes chemotherapy resistance. (ons.org)
- Researchers suspect that the BRCA2 protein has additional functions within cells. (medlineplus.gov)
- For example, the protein may help regulate cytokinesis, which is the step in cell division when the fluid surrounding the nucleus (the cytoplasm) divides to form two separate cells. (medlineplus.gov)
- Abnormally high expression of these genes rescued Brca2 loss-induced lethality in mES cells. (nih.gov)
- The altered gene encodes a protein called potassium chloride cotransporter 3 (KCC3), which helps swollen cells remove excess fluid. (nih.gov)
- The gene codes for the protein glucocerebrosidase, which normally helps cells dispose of certain lipids and other waste. (nih.gov)
- Cells that don't have any functioning BRCA1 or BRCA2 proteins can grow out of control and become cancer. (oncologica.com)
RAD512
- However, the localization of RAD51 to damage sites during TC-HR does not require BRCA1 and BRCA2, but relies on RAD52 and Cockayne Syndrome Protein B (CSB). (nature.com)
- The protein encoded by this gene is a member of the RAD51 protein family. (nih.gov)
Encodes1
- One candidate encodes a PDZ domain-containing protein, GIPC3. (nih.gov)
Researchers1
- A team of researchers led by Drs. Andre Nussenzweig and Shyam Sharan at NIH's National Cancer Institute (NCI) examined the roles of BRCA1 and BRCA2 in DNA replication, the process by which the cell copies DNA strands in preparation for cell division. (nih.gov)
20183
- HN - 2018(1987) MH - AAA Domain UI - D000074182 MN - G2.111.570.820.709.275.500.913 MS - An approximately 250 amino acid domain common to AAA ATPases and AAA Proteins. (nih.gov)
- HN - 2018 FX - ATPases Associated with Diverse Cellular Activities MH - AAA Proteins UI - D000074582 MN - D8.811.277.40.13 MN - D12.776.157.25 MS - A large, highly conserved and functionally diverse superfamily of NTPases and nucleotide-binding proteins that are characterized by a conserved 200 to 250 amino acid nucleotide-binding and catalytic domain, the AAA+ module. (nih.gov)
- and the management of co-occurring medical and psychiatric conditions HN - 2018 MH - ADP-Ribosylation UI - D000074744 MN - G2.111.660.871.790.600.200 MN - G2.111.691.600.200 MN - G3.734.871.790.600.200 MN - G5.308.670.600.200 MS - Post-translational modification of proteins with ADENOSINE DIPHOSPHATE RIBOSE. (nih.gov)
Replaces1
- A protein modification that effectively removes or replaces an L-glutamic acid. (reactome.org)
Function2
- Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
- When either of these genes is mutated, or altered, such that its protein product is not made or does not function correctly, DNA damage may not be repaired properly. (pvhomed.com)
Regulates1
- LMAN2 regulates the transport of exosomal cargo proteins through the Golgi complex [ 11 ]. (hindawi.com)
Enhances1
- When a patient with a BRCA2 mutation initially begins treatment, the mutation actually enhances the effect of chemotherapies such as cisplatin or olaparib. (ons.org)
Roles2
Cell3
- We used Gene Expression Profiling Interactive Analysis (GEPIA), Breast Cancer Gene-Expression Miner v4.7 (bc-GenExMiner v4.7), UALCAN, The Human Protein Atlas (HPA), Gene Expression-Based Outcome for Breast Cancer Online (GOBO), Cancer Cell Line Encyclopedia (CCLE), SpatialDB, and Tumor Immune Estimation Resource (TIMER) databases to evaluate the LMAN2 expression. (hindawi.com)
- Here we demonstrate that, in a specific vertebrate cell type, the chicken B cell line DT40, heterozygosity for a BRCA2 mutation has a distinct phenotype. (kent.ac.uk)
- Explore our solutions for multiple applications - vaccines, monoclonal antibodies, recombinant proteins, cell or gene therapy. (vwr.com)
Cancer6
- However, not everyone who inherits a mutation in the BRCA2 gene will develop cancer. (medlineplus.gov)
- The 29-year-old underwent a double mastectomy after testing positive for the BRCA2 gene mutation, which indicates an increased risk of breast cancer. (self.com)
- The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study. (cdc.gov)
- BRCA1 or BRCA2 are two different genes and the most common cause of hereditary breast cancer. (saintfrancishosp.com)
- There has been a lot of buzz recently about the BRCA1 and BRCA2 gene, also known as the breast cancer gene. (pvhomed.com)
- By contrast, according to the most recent estimates, 55 to 65 percent of women who inherit a harmful BRCA1 mutation and around 45 percent of women who inherit a harmful BRCA2 mutation will develop breast cancer by age 70 years. (pvhomed.com)
HUMAN1
- We are also examining the expression of GIPC3 in human BRCA2-deficient tumors. (nih.gov)
Risk1
- But fewer women are willing to consider prophylactic mastectomy, which markedly reduces risk in women with positive BRCA1 and BRCA2 tests. (pvhomed.com)
Damage1
- When a fork becomes stalled by DNA damage, BRCA1 and BRCA2 protect the newly synthesized strands of DNA. (nih.gov)
Patients1
- Clinical Decision-Making in Patients with Variant of Uncertain Significance in BRCA1 or BRCA2 Genes. (cdc.gov)
Type2
- LMAN2, a protein-coding gene, is responsible for encoding a type I transmembrane lectin that shuttles between the plasma membrane, Golgi apparatus, and endoplasmic reticulum. (hindawi.com)
- However, it is unclear whether loss of the wild type allele is stochastic or if heterozygosity for BRCA2 mutation carries a phenotype that contributes to tumorigenic progression. (kent.ac.uk)
Produce1
- BRCA1 and BRCA2 are genes that produce proteins that suppress tumors. (raphahl.com)
Positive1
- Murphy tested positive for the BRCA2 gene mutation , a rare mutation impacting less than 1 percent of the American population, according to the Susan G. Komen foundation . (self.com)