WBR0770
| Author | [[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Will Gibson)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Oncology |
| Prompt | [[Prompt::A 48-year-old woman, previously healthy, presents to the physician's office for a left breast lump she noticed on self-exam. She explains that she incidentally palpated the lump during showering. She does not complain of any pain or breast discharge. Following appropriate work-up, she is diagnosed with triple-negative breast cancer with ductal histology. Genetic analysis demonstrates a germline c.185delAG frameshift mutation in the BRCA1 gene. When asked, the physician explains the normal function of BRCA1. Which of the following best describes the molecular classification of the BRCA1 gene product?]] |
| Answer A | AnswerA::DNA repair protein |
| Answer A Explanation | AnswerAExp::BRCA1 and BRCA2 are tumor suppressor genes whose gene products are critical to repairing DNA double strand breaks. |
| Answer B | AnswerB::Transcription factor |
| Answer B Explanation | AnswerBExp::Examples of genes that encode transcription factors are C-myc, and N-myc, which are oncogenes associated with Burkitt's lymphoma, and neuroblastoma, respectively. |
| Answer C | AnswerC::Tyrosine kinase |
| Answer C Explanation | AnswerCExp::Examples of genes that encode tyrosine kinase are abl, HER2/neu, and ret oncogenes, which are associated with CML, breast cancer, and MEN II syndromes, respectively. |
| Answer D | AnswerD::GTPase |
| Answer D Explanation | [[AnswerDExp::An example of a gene that encodes GTPase is the ras proto-oncogene. Mutations of ras proteins abrogate GTAPase activity and force the protein to stay in the "on" GTP-bound state. Mutations of KRAS occur in pancreatic cancer (95%), colon cancer (40%) and lung cancer (20%).]] |
| Answer E | AnswerE::Cytokine receptor |
| Answer E Explanation | AnswerEExp::An example of a gene that encodes a cytokine receptor is c-kit oncogene that is associated with gastrointestinal stromal tumors (GIST). JAK1 is also a cytokine receptor that is mutated in polycythemia vera. |
| Right Answer | RightAnswer::A |
| Explanation | [[Explanation::BRCA1 and BRCA2 are tumor suppressor genes that are associated with breast cancer and ovarian cancer. Breast and many other tissues normally express BRCA1 to protect dividing cells from DNA damage. During replication, if one strand of DNA breaks a repair is easy; the opposing strand can be used as template. If both strands of DNA are broken (double strand break), a seamless repair is much more difficult as the intervening sequence can be ambiguous. There are two methods of resolving a double strand break: 1. Non-homologous end joining (NHEJ) and 2. Homologous recombination. NHEJ is an error-prone method in which random sequence is inserted and ligated to bridge the break. Conversely, homologous recombination uses homologous sequence from a sister chromatid as template to facilitate perfect repair. BRCA1 is a key coordinator of homologous recombination based pair. BRCA1 binds to a host of other proteins to form a complex that repairs DNA double strand break repairs by homologous recombination. When BRCA genes encode DNA repair proteins normally. Hence, their loss in cancers lead to inhibition of synthesis of DNA repair proteins and facilitation of cancer growth. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Breast, WBRKeyword::Cancer, WBRKeyword::Breast cancer, WBRKeyword::Oncogene, WBRKeyword::Tumor, WBRKeyword::Tumor suppressor, WBRKeyword::Tumor Suppressor gene, WBRKeyword::Genetics, WBRKeyword::DNA, WBRKeyword::DNA repair, WBRKeyword::BRCA1, WBRKeyword::BRCA2 |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |