A novel germline mutation in SDHA identified in a rare case of gastrointestinal stromal tumor complicated with renal cell carcinoma

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12188-97. eCollection 2015.

Abstract

Succinate dehydrogenase (SDH), which is located on the mitochondrial inner membrane, is essential to the Krebs cycle. Mutations of the SDH gene are associated with many tumors, such as renal cell carcinoma, wild type gastrointestinal stromal tumors (WT GISTs) and hereditary paragangliomas/pheochromocytomas. Herein we present a rare case diagnosed as a WT GIST complicated with a renal chromophobe cell tumor and detected a novel germline heterozygous mutation (c.2T>C: p.M1T) in the initiation codon of the SDHA gene. We also conduct a preliminary exploration for the mechanism of reduced expression of SDHB without mutation of SDHB gene. Our case enriches the mutation spectrum of the SDH gene. After reviewing previous studies, we found it to be the first case diagnosed as a WT GIST complicated with a synchronous renal chromophobe cell tumor and identified a novel germline heterozygous mutation. It was also the second reported case of a renal cell carcinoma associated with an SDHA mutation.

Keywords: Succinate dehydrogenase; gastrointestinal stromal tumor; mutation; renal cell carcinoma.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / complications
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Down-Regulation
  • Gastrointestinal Stromal Tumors / complications
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / pathology
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Heterozygote
  • Humans
  • Male
  • Paraganglioma, Extra-Adrenal / genetics*
  • Pheochromocytoma / genetics*
  • Succinate Dehydrogenase / genetics*
  • Young Adult

Substances

  • SDHD protein, human
  • Succinate Dehydrogenase