Familial Cancer

, Volume 11, Issue 2, pp 189–194

A novel germline SDHB mutation in a gastrointestinal stromal tumor patient without bona fide features of the Carney–Stratakis dyad

  • Ricardo Celestino
  • Jorge Lima
  • Alexandra Faustino
  • Valdemar Máximo
  • António Gouveia
  • João Vinagre
  • Paula Soares
  • José Manuel Lopes
Original Article

DOI: 10.1007/s10689-011-9499-x

Cite this article as:
Celestino, R., Lima, J., Faustino, A. et al. Familial Cancer (2012) 11: 189. doi:10.1007/s10689-011-9499-x

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchyme neoplasms of the gastrointestinal tract. Gain-of-function somatic mutations of the KIT or PDGFRA genes represent the most prevalent molecular alterations in GISTs. In Carney–Stratakis dyad, patients portray germline mutations of the succinate dehydrogenase subunits B (SDHB), C (SDHC) and D (SDHD) and develop multifocal GISTs and multicentric paragangliomas (PGLs). We herein report a novel germline SDHB mutation (c.T282A—Ile44Asn) occurring in a 26 years-old patient diagnosed with a spindle cell intermediate risk GIST that did not present KIT/PDGFRA/BRAF gene mutations. Further analyses revealed loss of the wild-type SDHB allele and complete loss of SDHB expression in the tumor tissue. After genetic screening of other family members, we detected in the patient′s mother a SDHB mutation without any clinical/laboratorial evidence of GIST or PGL. Altogether, our findings (germline SDHB mutation with absence of PGL in the index case and of GIST and/or PGL in his mother) raise the possibility that this familiar setting corresponds to an incomplete phenotype of the Carney–Stratakis dyad.

Keywords

Gastrointestinal stromal tumor SDH Carney–Stratakis dyad 

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Ricardo Celestino
    • 1
    • 2
    • 3
  • Jorge Lima
    • 1
    • 3
  • Alexandra Faustino
    • 1
  • Valdemar Máximo
    • 1
    • 3
  • António Gouveia
    • 3
    • 4
  • João Vinagre
    • 1
    • 2
    • 3
  • Paula Soares
    • 1
    • 3
  • José Manuel Lopes
    • 1
    • 3
    • 5
  1. 1.Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP)PortoPortugal
  2. 2.Institute of Biomedical Sciences Abel Salazar of the University of Porto (ICBAS)PortoPortugal
  3. 3.Medical FacultyUniversity of PortoPortoPortugal
  4. 4.Department of SurgeryHospital São JoãoPortoPortugal
  5. 5.Department of PathologyHospital São JoãoPortoPortugal