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. 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. Educational Objective: BRCA tumor suppressor genes encode DNA double strand break repair proteins. References: John, E. M., Miron, A., Gong, G., Phipps, A. I., Felberg, A., Li, F. P., ... & Whittemore, A. S. (2007). Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. Jama, 298(24), 2869-2876. First Aid 2015 page 236]]
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
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