Succinate dehydrogenase deficiency in a PDGFRA mutated GIST.

ABSTRACT:

Background

Most gastrointestinal stromal tumors (GISTs) harbor mutually exclusive gain of function mutations in the receptor tyrosine kinase (RTK) KIT (70-80%) or in the related receptor PDGFRA (~10%). These GISTs generally respond well to therapy with the RTK inhibitor imatinib mesylate (IM), although initial response is genotype-dependent. An alternate mechanism leading to GIST oncogenesis is deficiency in the succinate dehydrogenase (SDH) enzyme complex resulting from genetic or epigenetic inactivation of one of the four SDH subunit genes (SDHA, SDHB, SDHC, SDHD, collectively referred to as SDHX). SDH loss of function is generally seen only in GIST lacking RTK mutations, and SDH-deficient GIST respond poorly to imatinib therapy.

Methods

Tumor and normal DNA from a GIST ca

SUBMITTER: Belinsky MG 

PROVIDER: S-EPMC5541693 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature