WBR0065
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| Author | PageAuthor::William J Gibson (Reviewed by Yazan Daaboul) |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Oncology |
| Prompt | [[Prompt::A 32-year-old woman is contacted regarding an abnormal pap smear on her most recent annual screening exam. The smear shows dysplasia of squamous cells from the surface of the cervix. The degree of dysplasia is then deemed cervical intraepithelial neoplasia grade-1 (CIN-I). The molecular mechanism of oncogenesis of the causal organism is similar to the defect underlying which disease?]] |
| Answer A | AnswerA::Familial retinoblastoma |
| Answer A Explanation | AnswerAExp::Familial retinoblastoma is caused by mutations in the ''RB1'' gene that affect the Rb protein. HPV infection causes cervical cell dysplasia by expressing the E7 protein that sequesters and tags the ''RB1'' gene for degradation. |
| Answer B | AnswerB::Hereditary non-polyposis colorectal cancer (HNPCC) |
| Answer B Explanation | AnswerBExp::HPNCC is associated with germline mutations in several genes, such as ''MSH2'', ''MSH6'', and ''MLH1'' genes. |
| Answer C | AnswerC::Neurofibromatosis type I |
| Answer C Explanation | [[AnswerCExp::Neurofibromatosis is caused by mutations in the NF1 gene. Patients have café-au-lait spots, lisch nodules, optic gliomas, cutaneous neurofibromas, and endocrine tumors such as pheochromocytoma.]] |
| Answer D | AnswerD::Hereditary breast-ovarian cancer syndrome |
| Answer D Explanation | AnswerDExp::Hereditary breast-ovarian cancer syndrome (HBOC) is caused by mutations in the ''BRCA1'' and ''BRCA2'' genes. Female patients with these mutations have a 40%-80% lifetime risk of breast cancer and an 11%-40% lifetime risk of ovarian cancer. |
| Answer E | AnswerE::Cowden’s sydrome |
| Answer E Explanation | [[AnswerEExp::Cowden’s syndrome may be caused by loss-of-function mutations in the PTEN gene, a tumor suppressor gene.]] |
| Right Answer | RightAnswer::A |
| Explanation | [[Explanation::This young woman has an abnormal pap smear as a result of a previous infection with Human Papilloma Virus (HPV). HPV causes cervical dysplasia when the E6 and E7 proteins bind tumor suppressor proteins within the cell. E6 mediates the degradation of the tumor suppressor p53, which is also mutated in Li-Fraumeni syndrome. E7 binds to and inactivates RB gene, which is also mutated in familial retinoblastoma.
Rb protein normally acts as a sensor of DNA damage and cellular stress to stop cell cycle progression at the R (restriction) point between the G1 and S phases. Nonfunctional Rb protein leads to uninhibited progression through the cell cycle. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Microbiology, WBRKeyword::Cervical intraepithelial neoplasia, WBRKeyword::Cervix, WBRKeyword::Cervical cancer, WBRKeyword::Cervical, WBRKeyword::Virus, WBRKeyword::Viruses, WBRKeyword::DNA virus, WBRKeyword::DNA viruses, WBRKeyword::HPV, WBRKeyword::Cancer, WBRKeyword::Retinoblastoma, WBRKeyword::Tumor suppressor |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |