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SDHA Germline Mutations in SDH-Deficient GISTs: A Current Update.
Schipani, Angela; Nannini, Margherita; Astolfi, Annalisa; Pantaleo, Maria A.
Afiliación
  • Schipani A; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy.
  • Nannini M; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CS Utrecht, The Netherlands.
  • Astolfi A; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy.
  • Pantaleo MA; Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
Genes (Basel) ; 14(3)2023 03 04.
Article en En | MEDLINE | ID: mdl-36980917
ABSTRACT
Loss of function of the succinate dehydrogenase complex characterizes 20-40% of all KIT/PDGFRA-negative GIST. Approximately half of SDH-deficient GIST patients lack SDHx mutations and are caused by a hypermethylation of the SDHC promoter, which causes the repression of SDHC transcription and depletion of SDHC protein levels through a mechanism described as epimutation. The remaining 50% of SDH-deficient GISTs have mutations in one of the SDH subunits and SDHA mutations are the most common (30%), with consequent loss of SDHA and SDHB protein expression immunohistochemically. SDHB, SDHC, and SDHD mutations in GIST occur in only 20-30% of cases and most of these SDH mutations are germline. More recently, germline mutations in SDHA have also been described in several patients with loss of function of the SDH complex. SDHA-mutant patients usually carry two mutational events at the SDHA locus, either the loss of the wild type allele or a second somatic event in compound heterozygosis. This review provides an overview of all data in the literature regarding SDHA-mutated GIST, especially focusing on the prevalence of germline mutations in SDH-deficient GIST populations who harbor SDHA somatic mutations, and offers a view towards understanding the importance of genetic counselling for SDHA-variant carriers and relatives.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Tumores del Estroma Gastrointestinal Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Genes (Basel) Año: 2023 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Asunto principal: Tumores del Estroma Gastrointestinal Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Genes (Basel) Año: 2023 Tipo del documento: Article País de afiliación: Italia