Genetic Predisposition to Disease
Breast Neoplasms, Male
Neoplastic Syndromes, Hereditary
Tumor Suppressor Proteins
Fallopian Tube Neoplasms
Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1. (1/1487)Breast cancer 1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1) are multidomain proteins that interact in vivo via their N-terminal RING finger motif regions. To characterize functional aspects of the BRCA1/BARD1 interaction, we have defined the structural domains required for the interaction, as well as their oligomerization state, relative stability, and possible nucleic acid binding activity. We have found that the RING finger motifs do not themselves constitute stable structural domains but are instead part of larger domains comprising residues 1-109 of BRCA1 and residues 26-119 of BARD1. These domains exist as homodimers and preferentially form a stable heterodimer. Shorter BRCA1 RING finger constructs do not interact with BARD1 or with longer BRCA1 constructs, indicating that the heterodimeric and homodimer interactions are mediated by regions outside the canonical RING finger motif. Nucleic acid binding is a generally proposed function of RING finger domains. We show that neither the homodimers nor the heterodimer displays affinity for nucleic acids, indicating that the proposed roles of BRCA1 and BARD1 in DNA repair and/or transcriptional activation must be mediated either by other regions of the proteins or by additional cofactors. (+info)
Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1. (2/1487)An increasing number of transcription factors have been shown to activate DNA replication. However, the underlying mechanism remains to be elucidated. Here it is shown that when tethered to a cellular replication origin, the acidic transcriptional activation domain of the breast cancer protein BRCA1 alters the local chromatin structure and stimulates chromosomal DNA replication. Cancer-predisposing mutations in BRCA1 that abolish transcriptional activation also prevent chromatin remodeling and activation of replication. Chromatin remodeling occurs even in the absence of a functional replication origin. Thus, increasing chromatin accessibility may be an important mechanism used by transcription factors to facilitate multiple nuclear processes. (+info)
Should insurance pay for preventive services suggested by genetics? (3/1487)Physicians, plans and patients are discovering that the promise of genetic testing will be hard to fulfill. Even when a test can show predisposition toward a disease, performing it can't necessarily improve medical outcomes. Unfortunately, doing these tests can have some unintended negative effects. (+info)
BRCA1 and BRCA2 proteins: roles in health and disease. (4/1487)Between 5% and 10% of all breast cancer is hereditary, with patients having a strong family history of the disease. The remaining 90-95% of cases are classed as sporadic. Within the inherited group, 80-90% of cases are the result of germline mutations affecting two recently identified genes: BRCA1 and BRCA2. Since the sequencing of these genes, considerable research on the genetics of the mutation carriers has been performed, with less attention having been focused on the BRCA1 and BRCA2 proteins themselves. The structure and function of the protein products thus continues to hold mystery and might be the key to the full understanding of this complex disease. (+info)
Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage. (5/1487)Mutations in BRCA1 are responsible for nearly all of the hereditary ovarian and breast cancers, and about half of those in breast cancer-only kindreds. The ability of BRCA1 to transactivate the p21 promoter can be inactivated by mutation of the conserved BRCA1 C-terminal (BRCT) repeats. To explore the mechanisms of this BRCA1 function, the BRCT repeats were used as bait in a yeast two-hybrid screen. A known protein, CtIP, a co-repressor with CtBP, was found. CtIP interacts specifically with the BRCT repeats of BRCA1, both in vitro and in vivo, and tumor-derived mutations in this region abolished these interactions. The association of BRCA1 with CtIP was also abrogated in cells treated with DNA-damaging agents including UV, gamma-irradiation, and adriamycin, a response correlated with BRCA1 phosphorylation. The transactivation of the p21 promoter by BRCA1 was diminished by expression of exogenous CtIP and CtBP. These results suggest that the binding of the BRCT repeats of BRCA1 to CtIP/CtBP is critical in mediating transcriptional regulation of p21 in response to DNA damage. (+info)
Germline BRCA1 alterations in a population-based series of ovarian cancer cases. (6/1487)The objective of this study was to provide more accurate frequency estimates of breast cancer susceptibility gene 1 ( BRCA1 ) germline alterations in the ovarian cancer population. To achieve this, we determined the prevalence of BRCA1 alterations in a population-based series of consecutive ovarian cancer cases. This is the first population-based ovarian cancer study reporting BRCA1 alterations derived from a comprehensive screen of the entire coding region. One hundred and seven ovarian cancer cases were analyzed for BRCA1 alterations using the RNase mismatch cleavage assay followed by direct sequencing. Two truncating mutations, 962del4 and 3600del11, were identified. Both patients had a family history of breast or ovarian cancer. Several novel as well as previously reported uncharacterized variants were also identified, some of which were associated with a family history of cancer. The frequency distribution of common polymorphisms was determined in the 91 Caucasian cancer cases in this series and 24 sister controls using allele-specific amplification. The rare form of the Q356R polymorphism was significantly ( P = 0.03) associated with a family history of ovarian cancer, suggesting that this polymorphism may influence ovarian cancer risk. In summary, our data suggest a role for some uncharacterized variants and rare forms of polymorphisms in determining ovarian cancer risk, and highlight the necessity to screen for missense alterations as well as truncating mutations in this population. (+info)
Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. (7/1487)Germline mutations of the Brca1 tumor suppressor gene predispose women to breast and ovarian cancers. To study mechanisms underlying BRCA1-related tumorigenesis, we derived mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of the Brca1 gene. We show that the mutant cells maintain an intact G1-S cell cycle checkpoint and proliferate poorly. However, a defective G2-M checkpoint in these cells is accompanied by extensive chromosomal abnormalities. Mutant fibroblasts contain multiple, functional centrosomes, which lead to unequal chromosome segregation, abnormal nuclear division, and aneuploidy. These data uncover an essential role of BRCA1 in maintaining genetic stability through the regulation of centrosome duplication and the G2-M checkpoint and provide a molecular basis for the role of BRCA1 in tumorigenesis. (+info)
Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics. (8/1487)Reduced expression of BRCA1 has been reported in sporadic breast cancer, although the mechanisms underlying this phenomenon remain unclear. Abnormal methylation leading to silencing of tumour suppressor genes has been implicated in tumorigenesis in a wide range of sporadic cancers. Therefore, we sought to determine the frequency of methylation within the BRCA1 promoter region in a large group of sporadic invasive breast (n =96) and ovarian (n = 43) carcinomas using Southern analyses. Overall, methylation was detected in 11% of breast cancer cases and in 5% of ovarian tumours. Methylation of the BRCA1 promoter region was strongly correlated with lack of estrogen and progesterone receptor expression. It is clear from the frequency of abnormal methylation of the BRCA1 promoter region, that this cannot be the sole mechanism mediating the reduced expression of BRCA1 that has previously been reported to occur in the majority of invasive sporadic breast tumours. Nevertheless this study suggests that abnormal methylation of the BRCA1 promoter may be important in tumorigenesis in a subset of sporadic breast and ovarian cancers. (+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."
* Genetic mutations
* Hormonal imbalance
* Use of certain medications
* Alcohol consumption
* Swelling or lumps in the breast tissue
* Pain or tenderness in the breasts
* Nipple discharge
* Skin dimpling or puckering
* 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.
Tumor suppressor gene
Proximity ligation assay
Nucleolar and spindle associated protein 1
Fanconi anemia, complementation group C
60S ribosomal protein L31
Short interspersed nuclear element
Age and female fertility
Index of biochemistry articles
DNA damage theory of aging
Telomeric repeat-binding factor 2
Nuclear receptor coactivator 2
Breast cancer classification
Deficiency of RbAp48 protein and memory loss
Cell cycle checkpoint
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- Mutations in the BRCA1 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 BRCA1 gene mutations lead to the production of an abnormally short version of the BRCA1 protein or prevent any protein from being made from one copy of the gene. (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 BRCA1 gene mutations that increase the risk of breast cancer (described above) also increase the risk of ovarian cancer. (medlineplus.gov)
- Women with BRCA1 gene mutations have a 35 to 60 percent chance of developing ovarian cancer in their lifetimes, as compared with 1.6 percent in the general population. (medlineplus.gov)
- Inherited BRCA1 gene mutations have been found to increase the risk of prostate cancer. (medlineplus.gov)
- These mutations likely reduce the BRCA1 protein's ability to repair DNA, allowing potentially damaging mutations to persist in various other genes. (medlineplus.gov)
- Inherited mutations in the BRCA1 gene also increase the risk of several other types of cancer, including pancreatic cancer and colon cancer. (medlineplus.gov)
- These mutations impair the ability of the BRCA1 protein to help repair damaged DNA. (medlineplus.gov)
- It is not clear why different individuals with BRCA1 mutations develop cancers in different organs. (medlineplus.gov)
- Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. (medlineplus.gov)
- Molecular similarities between BLBCs and BRCA1-mutated tumors may therefore provide predictive markers for therapeutic response of BLBCs.Methods: There are several known molecular features characteristic for BRCA1-mutated breast tumors: 1) increased numbers of genomic aberrations, 2) a distinct pattern of genomic aberrations, 3) a high frequency of TP53 mutations and 4) a high incidence of complex, protein-truncating TP53 mutations. (vumc.nl)
- Together, BRCA1 and BRCA 2 mutations account for about 20-25% of hereditary breast cancers and 5-10% of all breast cancers. (nih.gov)
- Participants with history of germline BRCA1-Associated Protein-1 (BAP1) mutations. (nih.gov)
- Li and colleagues also evaluated this subset of women after excluding 92 patients who carried BRCA1/2 mutations, since these are known to be associated with poor prognosis, diagnosis at a younger age, estrogen receptor negativity, and basal-like subtype. (genomeweb.com)
- The researchers then analyzed genetic data from the 5,077 women who did not carry BRCA1/2 mutations with the polygenic risk score and found that a higher score was associated with less aggressive tumor phenotypes. (genomeweb.com)
- Inherited mutations in the breast and ovarian cancer susceptibility gene BRCA1 are associated with high risk for developing breast and ovarian cancers. (embl.de)
- Genetics plays a critical role in MM when the disease occurs in carriers of germline BRCA1 associated protein 1 mutations. (cdc.gov)
- PARP inhibitors (PARPis) are being used in patients with BRCA1/2 mutations. (tu-darmstadt.de)
- BRCA1 mutations are estimated to account for about a third of all inherited breast cancers and roughly 2-3 percent of all breast cancers. (ecancer.org)
- The mutations occur in exon 11 and proximal part of exon 12 and are strongly conserved at the protein level across various species. (biomedcentral.com)
- The BRCA2 protein, which has a function similar to that of BRCA1, also interacts with the RAD51 protein. (indiabix.com)
- Research suggests that the BRCA1 protein also regulates the activity of other genes and plays an essential role in embryonic development. (medlineplus.gov)
- Researchers discovered an unexpected way that breast cancers cells with mutant BRCA1 or BRCA2 genes acquire drug resistance and evade chemotherapies. (nih.gov)
- When either of these genes is mutated, or altered, the resulting abnormal proteins may be unable to properly repair DNA. (nih.gov)
- BRCA1 and BRCA2 genes create tumor-suppressing proteins and help repair damaged DNA. (self.com)
- Li and colleagues analyzed data from approximately 5,000 patients diagnosed with breast cancer between 2001 and 2008 in Sweden and evaluated their tumor characteristics and survival outcomes based on whether they had rare protein-truncating variants in 31 cancer predisposition genes. (genomeweb.com)
- Their evaluation showed that carriers of rare protein-truncating variants in any of the 31 cancer risk genes were more likely to develop high-grade tumors and not live as long as women who didn't carry such variants. (genomeweb.com)
- They found that women with rare protein-truncating variants in non-BRCA1/2 genes had 1.76 times the risk of death compared to non-carriers. (genomeweb.com)
- The set of DEs under investigation requires physicians and biologists to compare was extracted from eleven biomedical data their clinical and biological data to already exist- sources covering genes, proteins and diseases, ing data sets and to reference knowledge bases. (nih.gov)
- However, not everyone who inherits a mutation in the BRCA1 gene will develop cancer. (medlineplus.gov)
- Men who carry a BRCA1 gene mutation may also be at increased risk for other cancers, including breast and pancreatic cancer. (medlineplus.gov)
- Phenotypic features of BLBCs, such as clinical presentation and early age of onset, resemble those of breast tumors from BRCA1-mutation carriers. (vumc.nl)
- The reduced ability to repair DNA makes cancer cells with a BRCA1 or BRCA2 mutation sensitive to treatment with DNA-damaging drugs. (nih.gov)
- 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)
- Women who inherit a mutation in the gene that encodes BRCA1 have up to an 80 percent lifetime risk of developing breast cancer, several times the risk of those who don't have it, according to the National Cancer Institute. (ecancer.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)
- This is a Phase II study to determine the rate of stabilization or disease improvement from investigational decitabine/cedazuridine (INQOVI) treatment in subjects with BRCA1-Associated Protein-1 (BAP1) Cancer Predisposition Syndrome (CPDS) and subclinical, early-stage mesothelioma. (nih.gov)
- 7. BRCA1-associated protein (BAP1)-inactivated melanocytic tumors. (nih.gov)
- The genomic instability of BRCA1-mutated tumors can be effectively targeted with DNA-damaging agents and poly-(ADP-ribose) polymerase 1 (PARP1) inhibitors. (vumc.nl)
- BLBCs share molecular features that were previously found to be specific for BRCA1-mutated breast tumors. (vumc.nl)
- A deeper knowledge of the processes that drive drug resistance in BRCA1/2 -mutant tumors will lead to novel therapeutic approaches that target tumor-specific vulnerabilities," Nussenzweig adds. (nih.gov)
- However, doubly deficient BRCA1−/−53BP1−/− cells or tumors become resistant to PARPis. (tu-darmstadt.de)
- This review will focus on talazoparib, a PARP inhibitor approved by the US FDA for the treatment of metastatic g BRCA1/2 + breast cancers in October 2018. (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)
- Although BRCA1/2-associated cancers are often associated with worse tumor phenotypes, it has been documented that patients with breast cancer who are BRCA1 /2 carriers do not necessarily exhibit worse survival patterns than BRCA1/2 non-carriers," the authors wrote. (genomeweb.com)
- In the nucleus of many types of normal cells, the BRCA1 protein interacts with several other proteins to mend breaks in DNA. (medlineplus.gov)
- To carry out these functions, the BRCA1 protein interacts with many other proteins, including other tumor suppressors and proteins that regulate cell division. (medlineplus.gov)
- The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter. (embl.de)
- In the nucleus of many types of normal cells, the BRCA1 protein interacts with RAD51 during repair of DNA double-strand breaks. (indiabix.com)
- Previous studies emphasized the importance of the BRCT domain, which shows homology with p53 binding protein (53BP1), in transcriptional activation, growth inhibition and tumor suppression. (embl.de)
- VeraChem's protein-ligand binding free energy software VM2 used in the study "Characterization of Promiscuous Binding of Phosphor Ligands to Breast-Cancer-Gene 1 (BRCA1) C-Terminal (BRCT): Molecular Dynamics, Free Energy, Entropy and Inhibitor Design", PLoS Comput Biol 12 (8): e1005057. (verachem.com)
- The breast cancer susceptibility gene contains at its C terminus two copies of a conserved domain that was named BRCT for BRCA1 C terminus. (embl.de)
- The BRCT domain is not limited to the C-terminal of protein sequences and can be found in multiple copies or in a single copy as in RAP1 and TdT. (embl.de)
- Some data [ ( PUBMED:9799248 ) ] indicate that the BRCT domain functions as a protein-protein interaction module. (embl.de)
- There are 72534 BRCT domains in 52588 proteins in SMART's nrdb database. (embl.de)
- Taxonomic distribution of proteins containing BRCT domain. (embl.de)
- The complete taxonomic breakdown of all proteins with BRCT domain is also avaliable . (embl.de)
- Click on the protein counts, or double click on taxonomic names to display all proteins containing BRCT domain in the selected taxonomic class. (embl.de)
- In addition, the C-terminal second BRCA1 (BRCT) domain is sufficient for p53 mediated transactivation of the p21 promoter. (embl.de)
- The BRCA1 gene provides instructions for making a protein that acts as a tumor suppressor. (medlineplus.gov)
- 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)
- 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)
- The phosphoprotein encoded by the BRCA1 gene ( GENE, BRCA1 ). (nih.gov)
- The purpose of this Funding Opportunity Announcement (FOA) is to support multi-disciplinary projects aimed at the development of new targeted and effective therapies through systematic use and leveraging of recently identified genomic abnormalities and attendant changes in gene and/or protein expression profiles in human oral cancer samples. (nih.gov)
- PARP inhibitors are small molecule mimetics of nicotinamide which bind to PARP's catalytic domain to inhibit poly-ADP-ribosylation (PARylation) of target proteins, including PARP-1 itself. (nih.gov)
- SELDI-TOF protein profiles from this small pilot study distinguished between women with BRCA-1 Ca, Carriers, and women with SBC. (nih.gov)
- In agreement, a slightly stronger effect for worse survival was observed in carriers of non- BRCA1/2 protein-truncating variants after the removal of BRCA1/2 carriers. (genomeweb.com)
- BRCA1 splice variants BRCA1a (p110) and BRCA1b (p100) associates with CBP/p300 co-activators. (embl.de)
- Moreover, it appears likely that, in addition to BRCA1 associated protein 1, other yet unknown genetic variants may also influence the individual risk for development of MM, especially after exposure to asbestos and related mineral fibers. (cdc.gov)
- LMAN2 regulates the transport of exosomal cargo proteins through the Golgi complex [ 11 ]. (hindawi.com)
Involved in DNA repair1
- The BRCA1 and BRCA2 proteins are involved in DNA repair by homologous recombination. (nih.gov)
- These results demonstrate for the first time the presence of a second p53 interaction domain in BRCA1 proteins and suggests that BRCA1a and BRCA1b proteins, like BRCA1, function as p53 co-activators. (embl.de)
- Selecting all the terms (extracted from ers about proteins: Swiss-Prot7, PDB8, HPRD9, the different HTML pages) common to at Interpro10 or diseases: OMIM11. (nih.gov)
- By helping to repair DNA, the BRCA1 protein plays a critical role in maintaining the stability of a cell's genetic information. (medlineplus.gov)
- Surfaced-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) differentiation of serum protein profiles of BRCA-1 and sporadic breast cancer. (nih.gov)
- These effects are counteracted by the AhR-antagonist alpha-naphthoflavone (ANF), and in breast cancer cells expressing mutant p53 or the E6 human papilloma virus protein. (nih.gov)
- In the cohort of 5,099 breast cancer patients, 597 women carried a rare protein-truncating variant. (genomeweb.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. (nih.gov)
- 246-646 HOST SPECIES: Rabbit SPECIES REACTIVITY: Human, Rat IMMUNOGEN: Recombinant fusion protein containing a sequence corresponding to amino acids 1-195 of human. (gen9bio.com)
- In-silico analyses using PolyPhen-2 and SIFT predict the amino acid substitutions to be potentially deleterious to the protein function. (biomedcentral.com)
Maintaining the stability1
- By influencing DNA damage repair, these three proteins play a role in maintaining the stability of the human genome. (indiabix.com)
- BRCA1 and BRCA2 are human proteins that help to repair damaged DNA. (nih.gov)
- 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)
- The researchers identified several proteins that actively promote destabilization of replication forks. (nih.gov)
- VeraChem's state of the art computational chemistry software is capable of protein-ligand and host-guest binding affinity prediction, fast calculation of accurate partial atomic charges for drug-like compounds, computation of energies and forces with empirical force fields, automatic generation of alternate resonance forms of drug-like compounds, conformational search with the powerful Tork distort-minimize algorithm, and automatic detection of topological and 3D molecular symmetries. (verachem.com)
- Certain proteins are recruited to stalled forks to stabilize, repair, and restart the replication fork. (nih.gov)
- Their absence protected the DNA at replication forks and reversed the drug sensitivity of BRCA1- and BRCA2- mutant cells. (nih.gov)
- Loss of Artemis restores PARPi resistance in BRCA1-deficient cells. (tu-darmstadt.de)
- The sera were spotted onto protein chips for SELDI-TOF analysis and analyzed with classification algorithm software. (nih.gov)
- Until recently, scientists thought methylation enzymes acted only on DNA molecules or on histones, proteins that bundle DNA into spool-like packages. (ecancer.org)
- Our findings demonstrate an additional function for this domain in protein-protein interaction and co-activation of p53. (embl.de)
- It contains an N-terminal RING FINGER DOMAIN and is a PROTEIN PHOSPHATASE 1 regulatory subunit. (nih.gov)
- Also, the methylation appears in exactly the same spot where another protein called BRCA1 adds a different kind of regulatory marking, and may block BRCA1's restrictive effects on the oestrogen receptor. (ecancer.org)
- 13-ORB312690 Product Name: PCV2 Cap protein antibody Catalog Number: orb312690 Species/Host: Rabbit. (gen9bio.com)
- These results suggest that one of the mechanisms by which BRCA1 proteins function is through recruitment of CBP/p300 associated HAT/FAT activity for acetylation of p53 to specific promoters resulting in transcriptional activation. (embl.de)
- We also found that BRCA1a and BRCA1b proteins interact with p53 in vitro and in vivo. (embl.de)
- Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) profiling can differentiate protein signatures of cancer and normal subjects. (nih.gov)
- Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. (medlineplus.gov)