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BRCA1 and BRCA2, Inherited Germline Mutations

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Expand Collapse BRCA1 and BRCA2  - General Description BRCA1 and BRCA2 are genes that encode proteins that play an important role in DNA repair. DNA is damaged in organisms through various means-UV from the sunlight, and exposure to other substances that cause breaks or cross-links in the DNA. DNA breaks also occur when cells are dividing and chromosomes need to separate, especially in cells that will eventually have half the number of chromosomes-the egg and sperm-during a process called meiosis. When the proteins that are involved in DNA repair are mutated or missing, breaks in the DNA do not get repaired, resulting in an accumulation of DNA that is incorrectly arranged, which leads to cancer. For this reason, BRCA1 and BRCA2 are called tumor suppressor genes, because when they function correctly, they participate in repairing DNA and preventing cancers. When both strands of the DNA helix are disrupted, a process called Double Stranded DNA Repair takes place through a process called Homologous Recombination. This process involves a complex-or group-of many different proteins, some that attach onto the broken ends of DNA and then recruit other proteins to the site that are able to repair double strand breaks (DSB's) in the DNA so that the genes they encode are correctly sequenced when the repair is complete. Along with the BRCA proteins, proteins called RAD50 and RAD51 are part of the complex of proteins involved in DNA repair. During the DNA repair process, BRCA2 recruits RAD51 into the complex that is responsible for DNA repair. BRCA1 and BRCA2 are genes that were discovered in families that had a high incidence of breast cancer. In these families, the genetic alterations in BRCA1 or BRCA2 are present in the germ-line, which means they are inherited. Inherited germ-line mutations in BRCA1 or BRCA2 greatly increase the likelihood of developing cancer of the breast or ovary, as well as prostate cancer in men. BRCA1 has many functions in the cell. It is involved in transcription of genes, targeting proteins for degradation in the cell, cell cycle regulation, and homologous recombination to repair DNA. BRCA2 is involved in homologous recombination to repair DNA. When either BRCA gene is missing or inactivated, the result is hereditary breast and ovarian cancer (HBOC). BRCA2 mutations confer a 50-60% lifetime risk of breast cancer, a 30% lifetime risk of ovarian cancer, a 20 fold risk of prostate cancer, a tenfold risk of pancreatic cancer, and potentially increased frequency of other cancers as well. Patients can also develop somatic mutations or deletions of the BRCA1 or BRCA2 gene during their lifetime, instead of inheriting these mutations. Spontaneous mutations in BRCA1 or BRCA2 in an individual are called sporadic mutations. As more patients with different tumor types are tested for BRCA1 and BRCA2, it is becoming evident that multiple tumor types can harbor BRCA1 or BRCA2 mutations or deletions of the gene. Mutations in other genes involved in DNA repair can also contribute to the development of tumors. Testing is available for BRCA1 and BRCA2 mutations at MGH, where there are established treatments such as PARP inhibitors in use, and clinical trials ongoing for improved treatments for patients carrying these mutations. Sources: The DNA Damage Response: Ten Years After, J. Wade Harper, Stephen J. Elledge, Molecular Cell, Vol.28, Issue 5, 2007, pages 739-745. DNA repair targeted therapy: The past or future of cancer treatment? 2017 Science Direct article pii/S0163725816000322BRCA1 and BRCA2 are genes that encode proteins that play an important role in DNA repair. DNA is damaged in organisms through various means-UV from the sunlight, and exposure to other substances that cause breaks or cross-links in the DNA. DNA breaks also occur when cells are dividing and chromosomes need to separate, especially in cells that will eventually have half the number of chromosomes-the egg and sperm-during a process called meiosis. When the proteins that are involved in DNA repair are mutated or missing, breaks in the DNA do not get repaired, resulting in an accumulation of DNA that is incorrectly arranged, which leads to cancer. For this reason, BRCA1 and BRCA2 are called tumor suppressor genes, because when they function correctly, they participate in repairing DNA and preventing cancers. When both strands of the DNA helix are disrupted, a process called Double Stranded DNA Repair takes place through a process called Homologous Recombination. This process involves a complex-or group-of many different proteins, some that attach onto the broken ends of DNA and then recruit other proteins to the site that are able to repair double strand breaks (DSB's) in the DNA so that the genes they encode are correctly sequenced when the repair is complete. Along with the BRCA proteins, proteins called RAD50 and RAD51 are part of the complex of proteins involved in DNA repair. During the DNA repair process, BRCA2 recruits RAD51 into the complex that is responsible for DNA repair. BRCA1 and BRCA2 are genes that were discovered in families that had a high incidence of breast cancer. In these families, the genetic alterations in BRCA1 or BRCA2 are present in the germ-line, which means they are inherited. Inherited germ-line mutations in BRCA1 or BRCA2 greatly increase the likelihood of developing cancer of the breast or ovary, as well as prostate cancer in men. BRCA1 has many functions in the cell. It is involved in transcription of genes, targeting proteins for degradation in the cell, cell cycle regulation, and homologous recombination to repair DNA. BRCA2 is involved in homologous recombination to repair DNA. When either BRCA gene is missing or inactivated, the result is hereditary breast and ovarian cancer (HBOC). BRCA2 mutations confer a 50-60% lifetime risk of breast cancer, a 30% lifetime risk of ovarian cancer, a 20 fold risk of prostate cancer, a tenfold risk of pancreatic cancer, and potentially increased frequency of other cancers as well. Patients can also develop somatic mutations or deletions of the BRCA1 or BRCA2 gene during their lifetime, instead of inheriting these mutations. Spontaneous mutations in BRCA1 or BRCA2 in an individual are called sporadic mutations. As more patients with different tumor types are tested for BRCA1 and BRCA2, it is becoming evident that multiple tumor types can harbor BRCA1 or BRCA2 mutations or deletions of the gene. Mutations in other genes involved in DNA repair can also contribute to the development of tumors. Testing is available for BRCA1 and BRCA2 mutations at MGH, where there are established treatments such as PARP inhibitors in use, and clinical trials ongoing for improved treatments for patients carrying these mutations. Sources: The DNA Damage Response: Ten Years After, J. Wade Harper, Stephen J. Elledge, Molecular Cell, Vol.28, Issue 5, 2007, pages 739-745. DNA repair targeted therapy: The past or future of cancer treatment? 2017 Science Direct article pii/S0163725816000322
BRCA1 and BRCA2 are genes that encode proteins that play an important role in DNA repair. DNA is damaged in organisms through various means-UV from the sunlight, and exposure to other substances that cause breaks or cross-links in the DNA. DNA breaks also occur when cells are dividing and chromosomes need to separate, especially in cells that will eventually have half the number of chromosomes-the egg and sperm-during a process called meiosis. When the proteins that are involved in DNA repair are mutated or missing, breaks in the DNA do not get repaired, resulting in an accumulation of DNA that is incorrectly arranged, which leads to cancer. For this reason, BRCA1 and BRCA2 are called tumor suppressor genes, because when they function correctly, they participate in repairing DNA and preventing cancers.

When both strands of the DNA helix are disrupted, a process called Double Stranded DNA Repair takes place through a process called Homologous Recombination. This process involves a complex-or group-of many different proteins, some that attach onto the broken ends of DNA and then recruit other proteins to the site that are able to repair double strand breaks (DSB's) in the DNA so that the genes they encode are correctly sequenced when the repair is complete. Along with the BRCA proteins, proteins called RAD50 and RAD51 are part of the complex of proteins involved in DNA repair. During the DNA repair process, BRCA2 recruits RAD51 into the complex that is responsible for DNA repair.

BRCA1 and BRCA2 are genes that were discovered in families that had a high incidence of breast cancer. In these families, the genetic alterations in BRCA1 or BRCA2 are present in the germ-line, which means they are inherited. Inherited germ-line mutations in BRCA1 or BRCA2 greatly increase the likelihood of developing cancer of the breast or ovary, as well as prostate cancer in men. BRCA1 has many functions in the cell. It is involved in transcription of genes, targeting proteins for degradation in the cell, cell cycle regulation, and homologous recombination to repair DNA. BRCA2 is involved in homologous recombination to repair DNA. When either BRCA gene is missing or inactivated, the result is hereditary breast and ovarian cancer (HBOC). BRCA2 mutations confer a 50-60% lifetime risk of breast cancer, a 30% lifetime risk of ovarian cancer, a 20 fold risk of prostate cancer, a tenfold risk of pancreatic cancer, and potentially increased frequency of other cancers as well.

Patients can also develop somatic mutations or deletions of the BRCA1 or BRCA2 gene during their lifetime, instead of inheriting these mutations. Spontaneous mutations in BRCA1 or BRCA2 in an individual are called sporadic mutations. As more patients with different tumor types are tested for BRCA1 and BRCA2, it is becoming evident that multiple tumor types can harbor BRCA1 or BRCA2 mutations or deletions of the gene. Mutations in other genes involved in DNA repair can also contribute to the development of tumors. Testing is available for BRCA1 and BRCA2 mutations at MGH, where there are established treatments such as PARP inhibitors in use, and clinical trials ongoing for improved treatments for patients carrying these mutations.

Sources:
The DNA Damage Response: Ten Years After, J. Wade Harper, Stephen J. Elledge, Molecular Cell, Vol.28, Issue 5, 2007, pages 739-745.

DNA repair targeted therapy: The past or future of cancer treatment? 2017
Science Direct article pii/S0163725816000322
BRCA1 and BRCA2 are genes that encode proteins that play an important role in DNA repair. DNA is damaged in organisms through various means-UV from the sunlight, and exposure to other substances that cause breaks or cross-links in the DNA. DNA breaks also occur when cells are dividing and chromosomes need to separate, especially in cells that will eventually have half the number of chromosomes-the egg and sperm-during a process called meiosis. When the proteins that are involved in DNA repair are mutated or missing, breaks in the DNA do not get repaired, resulting in an accumulation of DNA that is incorrectly arranged, which leads to cancer. For this reason, BRCA1 and BRCA2 are called tumor suppressor genes, because when they function correctly, they participate in repairing DNA and preventing cancers.

When both strands of the DNA helix are disrupted, a process called Double Stranded DNA Repair takes place through a process called Homologous Recombination. This process involves a complex-or group-of many different proteins, some that attach onto the broken ends of DNA and then recruit other proteins to the site that are able to repair double strand breaks (DSB's) in the DNA so that the genes they encode are correctly sequenced when the repair is complete. Along with the BRCA proteins, proteins called RAD50 and RAD51 are part of the complex of proteins involved in DNA repair. During the DNA repair process, BRCA2 recruits RAD51 into the complex that is responsible for DNA repair.

BRCA1 and BRCA2 are genes that were discovered in families that had a high incidence of breast cancer. In these families, the genetic alterations in BRCA1 or BRCA2 are present in the germ-line, which means they are inherited. Inherited germ-line mutations in BRCA1 or BRCA2 greatly increase the likelihood of developing cancer of the breast or ovary, as well as prostate cancer in men. BRCA1 has many functions in the cell. It is involved in transcription of genes, targeting proteins for degradation in the cell, cell cycle regulation, and homologous recombination to repair DNA. BRCA2 is involved in homologous recombination to repair DNA. When either BRCA gene is missing or inactivated, the result is hereditary breast and ovarian cancer (HBOC). BRCA2 mutations confer a 50-60% lifetime risk of breast cancer, a 30% lifetime risk of ovarian cancer, a 20 fold risk of prostate cancer, a tenfold risk of pancreatic cancer, and potentially increased frequency of other cancers as well.

Patients can also develop somatic mutations or deletions of the BRCA1 or BRCA2 gene during their lifetime, instead of inheriting these mutations. Spontaneous mutations in BRCA1 or BRCA2 in an individual are called sporadic mutations. As more patients with different tumor types are tested for BRCA1 and BRCA2, it is becoming evident that multiple tumor types can harbor BRCA1 or BRCA2 mutations or deletions of the gene. Mutations in other genes involved in DNA repair can also contribute to the development of tumors. Testing is available for BRCA1 and BRCA2 mutations at MGH, where there are established treatments such as PARP inhibitors in use, and clinical trials ongoing for improved treatments for patients carrying these mutations.

Sources:
The DNA Damage Response: Ten Years After, J. Wade Harper, Stephen J. Elledge, Molecular Cell, Vol.28, Issue 5, 2007, pages 739-745.

DNA repair targeted therapy: The past or future of cancer treatment? 2017
Science Direct article pii/S0163725816000322
PubMed ID's
19553641,
Expand Collapse Inherited Germline Mutations  in BRCA1 and BRCA2
The loss or inactivation of BRCA1 or BRCA2 genes have a serious impact on the cells ability to repair DNA damage when it occurs. In familial cancer syndromes, BRCA1 or BRCA2 genes are lost or impaired in the germline, meaning the defect in the gene is inherited. Inherited BRCA1 or BRCA2 impairment causes an increased risk of developing cancer.
The loss or inactivation of BRCA1 or BRCA2 genes have a serious impact on the cells ability to repair DNA damage when it occurs. In familial cancer syndromes, BRCA1 or BRCA2 genes are lost or impaired in the germline, meaning the defect in the gene is inherited. Inherited BRCA1 or BRCA2 impairment causes an increased risk of developing cancer.

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Your Matched Clinical Trials

Trial Matches: (G) - Gene, (M) - Mutation
Trial Status: Showing all 1 result Per Page:
Protocol # Title Location Status Match
NCT01525589 A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer MGH Open GM
MGH has many open clinical trials for other cancers not shown on the Targeted Cancer Care website. They can be found on the MassGeneral.org clinical trials search page.

Additional clinical trials may be applicable to your search criteria, but they may not be available at MGH. These clinical trials can typically be found by searching the clinicaltrials.gov website.
Trial Status: Showing all 1 result Per Page:

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