WBR0065

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics, MainCategory::Microbiology
Sub Category	SubCategory::Oncology, SubCategory::General Principles, SubCategory::Infectious Disease
Prompt	[[Prompt::A 20-year-old woman is contacted regarding an abnormal pap smear on her last annual physical. The smear showed dysplasia of squamous cells from the surface of the cervix. The degree of dysplasia is deemed cervical intraepithelial neoplasia grade 1 (CIN1). 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. HPV infection causes cervical cell dysplasia by expressing the E7 protein that sequesters and tags the RB1 gene for degradation.
Answer B	AnswerB::Familial adenomatous polyposis
Answer B Explanation	AnswerBExp::Familial adenomatous polyposis (FAP) is caused by mutations in the APC gene. These patients develop thousands of polyps in their colons by the third decade of life.
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 and cutaneous neurofibromas.]]
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 is caused by mutations in the PTEN gene.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::This young woman has an abnormal pap smear as a result of 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 mutated in Li-Fraumeni syndrome. E7 binds to and inactivates Rb which is 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 G1 and S phase. Nonfunctional Rb leads to uninhibited progression through the cell cycle. Educational Objective: HPV causes oncogenesis when E7 binds to and inactivates Rb which is mutated in familial retinoblastoma. References: First Aid 2014 page 579 First Aid 2012 page 543]]
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
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