GTS5:BRCA-related cancer predisposition syndrome (BRCA1, BRCA2)
Primary Author(s)*
Katherine Geiersbach, MD, Mayo Clinic - Rochester, MN, USA
WHO Classification of Disease
(Instructions: This table’s content from the WHO book will be autocompleted.)
| Structure | Disease |
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| Book | |
| Category | |
| Family | |
| Type | |
| Subtype(s) |
Related Terminology
(Instructions: This table will have the related terminology from the WHO book autocompleted.)
| Acceptable | |
| Not Recommended |
Definition/Description of Disease
Put your text here (Instructions: Include a brief general clinical description, diagnostic criteria, and differential diagnosis if applicable. Include disease context relative to other WHO classification categories, i.e. describe any information relevant to the genetic aspects of the disease from all WHO classification books in which the syndrome is described.)
Epidemiology/Prevalence
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Genetic Abnormalities: Germline
Put your text here and fill in the table (Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.)
| Gene | Genetic Variant or Variant Type | Molecular Pathogenesis | Inheritance, Penetrance, Expressivity | Notes |
|---|---|---|---|---|
| BRCA1 | Many | EXAMPLE: Multiple variant types leading to loss of function | EXAMPLE: Autosomal recessive,
~30% penetrant for carriers |
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| BRCA2 | EXAMPLE: List the specific mutation | |||
Genetic Abnormalities: Somatic
Put your text here and fill in the table (Instructions: Describe significant second hit mutations, or somatic variants that present as a germline syndrome. In the notes, include details about most common mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetic-related information. Please include references throughout the table. Do not delete the table.)
| Gene | Genetic Variant or Variant Type | Molecular Pathogenesis | Inheritance, Penetrance, Expressivity | Notes |
|---|---|---|---|---|
| EXAMPLE: BRCA1 | EXAMPLE: Biallelic inactivation variants | EXAMPLE: Second hit mutation can occur as copy neutral LOH, inactivating mutation, deletion, promoter hypermethylation, or a structural abnormality disrupting the gene. | ||
| EXAMPLE: BRCA1 | EXAMPLE: Reversion mutation | EXAMPLE: After exposure to certain therapies (e.g. PARP inhibitors), a second mutation may restore gene function as a resistance mechanism. | ||
Genes and Main Pathways Involved
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| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
Genetic Diagnostic Testing Methods
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Additional Information
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Links
References
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Notes
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Prior Author(s):