Chapter 28 - The Genetic Basis of Cancer of the Kidney

Abstract

This chapter discusses the genetic basis of cancer of the kidney. The hereditary renal cancer syndromes include von Hippel-Lindau (VHL), hereditary papillary renal cancer (HPRC), Birt-Hogg-Dubé (BHD), and hereditary leiomyomatosis and renal cell cancer (HLRCC). Von Hippel-Lindau is an autosomal dominantly inherited disorder that leads to development of hemangioblastomas of the central nervous system (CNS), endolymphatic sac tumors, pancreatic cysts and neoplasms, pheochromocytomas, renal cysts and cancers, and cystadenomas of the epididymis and broad ligament. Hemangioblastomas of the CNS are the most common manifestation of VHL. These are most commonly found in the spinal cord and cerebellum. These are benign tumors, but can cause much morbidity. Lesions are resected when they become symptomatic. HPRC is an autosomal dominant syndrome with high penetrance marked by the predisposition of patients to form multifocal, bilateral renal tumors of papillary type I pathology. The tumors often appear later than in other hereditary renal cancer syndromes, with onset in the 4th, 5th, and 6th decades of life. Patients with HPRC have mutations in the tyrosine kinase domain of the METgene, located on chromosome 7q31, which is postulated to be an activating mutation, unlike VHL, a tumor suppressor gene. METencodes a tyrosine kinase activated by hepatocyte growth factor (HGF). The Birt-Hogg-Dubé syndrome is an autosomal dominant disorder in which affected individuals develop benign cutaneous tumors, pulmonary air-filled cysts and spontaneous pneumothoraces, and renal neoplasms. The hallmark lesion of BHD is the fibrofolliculoma, a benign tumor of the hair follicle, which appears in the third to fourth decade of life.