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.
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Acknowledgments
This study was supported by Fundação Calouste Gulbenkian through a PhD grant to R.C.; by Fundação para a Ciência e Tecnologia through the program Ciência 2007 (V.M.) and 2008 (J.L.) and Novartis through a project grant. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education that is partially supported by the FCT.
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Celestino, R., Lima, J., Faustino, A. et al. A novel germline SDHB mutation in a gastrointestinal stromal tumor patient without bona fide features of the Carney–Stratakis dyad. Familial Cancer 11, 189–194 (2012). https://doi.org/10.1007/s10689-011-9499-x
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DOI: https://doi.org/10.1007/s10689-011-9499-x