Molecular alterations and expression of succinate dehydrogenase complex in wild-type KIT/PDGFRA/BRAF gastrointestinal stromal tumors

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Ricardo Celestino (Author) Other; Jorge Lima (Author) FMUP; Alexandra Faustino (Author) Other; Joao Vinagre (Author) Other; Valdemar Maximo (Author) FMUP; Antonio Gouveia (Author) Other; Paula Soares (Author) FMUP; Jose Manuel Lopes (Author) FMUP

Journal

Title: European Journal of Human Genetics

Vol. 21

Pages: 503-510

ISSN: 1018-4813

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 18 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-005-1A6

DOI: 10.1038/ejhg.2012.205

Abstract (EN): Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, disclosing somatic KIT, PDGFRA and BRAF mutations. Loss of function of succinate dehydrogenase (SDH) complex is an alternative molecular mechanism in GISTs, namely in carriers of germline mutations of the SDH complex that develop Carney-Stratakis dyad characterized by multifocal GISTs and multicentric paragangliomas (PGLs). We studied a series of 25 apparently sporadic primary wild-type (WT) KIT/PDGFRA/BRAF GISTs occurring in patients without personal or familial history of PGLs, re-evaluated clinicopathological features and analyzed molecular alterations and immunohistochemistry expression of SDH complex. As control, we used a series of well characterized 49 KIT/PDGFRA/BRAF-mutated GISTs. SDHB expression was absent in 20% and SDHB germline mutations were detected in 12% of WT GISTs. Germline SDHB mutations were significantly associated to younger age at diagnosis. A significant reduction in SDHB expression in WT GISTs was found when compared with KIT/PDGFRA/BRAF-mutated GISTs. No significant differences were found when comparing DOG-1 and c-KIT expression in WT, SDHB-mutated and KIT/PDGFRA/BRAF-mutated GISTs. Our results confirm the occurrence of germline SDH genes mutations in isolated, apparently sporadic WT GISTs. WT KIT/PDGFRA/BRAF GISTs without SDHB or SDHA/SDHB expression may correspond to Carney-Stratakis dyad or Carney triad. Most importantly, the possibility of PGLs (Carney-Stratakis dyad) and/or pulmonary chondroma (Carney triad) should be addressed in these patients and their kindred. European Journal of Human Genetics (2013) 21, 503-510; doi:10.1038/ejhg.2012.205; published online 5 September 2012

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8