A 60-year-old man comes to the office due to dark, rusty-colored urine for the last 2 weeks. He reports no pain, urinary frequency, or urgency. The patient has no chronic medical conditions and takes no medications. He smoked a half pack of cigarettes daily for 10 years but quit 30 years ago. His father had hypertension and his mother has Alzheimer dementia. Urinalysis shows a large number of red blood cells. Renal ultrasound reveals a mass in the right kidney. Cytologic evaluation of the mass shows malignant cells with a chromosome 3p deletion. The deletion most likely involves which of the following genes?

Question

A 60-year-old man comes to the office due to dark, rusty-colored urine for the last 2 weeks.  He reports no pain, urinary frequency, or urgency.  The patient has no chronic medical conditions and takes no medications.  He smoked a half pack of cigarettes daily for 10 years but quit 30 years ago.  His father had hypertension and his mother has Alzheimer dementia.  Urinalysis shows a large number of red blood cells.  Renal ultrasound reveals a mass in the right kidney.  Cytologic evaluation of the mass shows malignant cells with a chromosome 3p deletion.  The deletion most likely involves which of the following genes?

Quizplus · Accepted Answer

11ec160b_3789_029c_9249_cff41bcb6a3c_MD0001_00 This patient with hematuria and a malignant renal mass most likely has renal cell carcinoma (RCC). RCC, particularly the clear cell subtype, is strongly associated with deletion, nonsense, and frameshift mutations involving the von Hippel-Lindau (VHL) gene at chromosome 3p. The majority of RCCs are sporadic and develop as single tumors; these are typically associated with somatic mutations in the VHL gene. Germline VHL mutations also occur and are responsible for von Hippel-Lindau syndrome, a rare, autosomal dominant disorder characterized by clear cell renal carcinomas (often multifocal and bilateral), cerebellar hemangioblastoma, and pheochromocytoma. VHL encodes a protein that normally inhibits hypoxia-inducible factors; VHL mutations lead to constitutive activation of these proteins, resulting in overexpression of multiple angiogenic growth factors (eg, VEG-F, PDG-F) that stimulate tumor proliferation. As a result, tumors harboring VHL mutations are highly sensitive to angiogenesis inhibitors. (Choice A) c-MYC is an oncogene located on chromosome 8. Mutations are associated with Burkitt lymphoma and diffuse large B-cell lymphoma. (Choice B) NF-1 is a tumor suppressor gene located on chromosome 17. Mutations of this gene cause neurofibromatosis type 1. (Choice C) The RB tumor suppressor gene (antioncogene) is located on chromosome 13. Mutations of this gene lead to the development of retinoblastoma and osteosarcoma. (Choice E) Mutations of the WT-1 tumor suppressor gene are associated with the development of Wilms tumor. This gene is located on chromosome 11. Educational objective: Sporadic and hereditary (associated with von Hippel-Lindau disease) renal cell carcinomas are associated with mutations involving the VHL gene on chromosome 3p. The VHL gene is a tumor suppressor that inhibits hypoxia-inducible factors; mutations lead to constitutive activation of these proteins, resulting in the activation of multiple angiogenic and tumorigenic growth factors (eg, VEG-F, PDG-F). __________ References: VHL and hypoxia signaling: beyond HIF in cancer. (http://www.ncbi.nlm.nih.gov/pubmed/29562667)

A 60-Year-Old Man Comes to the Office Due to Dark