Researchers Identify 3 GIST Molecular Subtypes With Prognostic Implications

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Researchers have identified 3 new molecular subtypes in gastrointestinal stromal tumors that have implications for prognosis.
Researchers have identified 3 new molecular subtypes in gastrointestinal stromal tumors that have implications for prognosis.

Researchers have identified 3 new molecular subtypes in gastrointestinal stromal tumors (GISTs) that have implications for prognosis and clinical management, a study published in JAMA Oncology has shown.1

Wild-type (WT) GISTs, which lack KIT and PDGFRA gene mutations, are the primary form of GIST in children and sometimes occur in adults; however, these patients respond poorly to standard targeted therapy like imatinib. Therefore, researchers sought to evaluate the clinical and tumor genomic features of WT GIST to ultimately improve management of these difficult-to-treat tumors.

For the observational study, researchers enrolled 116 patients with WT GIST, of which 95 had adequate tumor specimens available. Beginning in 2008, patients were evaluated in a GIST clinic once or twice yearly.

Researchers characterized their tumors by immunohistochemical analysis (IHC) for succinate dehydrogenase (SDH) subunit B, sequencing of SDH genes, and determination of SDHC promoter methylation.

Patients were classified into 3 molecular subtypes: SDH-competent, defined by detection of SDHB by IHC; and 2 types of SDH-deficient GIST. Researchers found that 63 of the 84 SDH-deficient tumors had SDH mutations and 31 had the SDHX mutation in germline. Further, 21 SDH-deficient tumors had SDHC promoter methylation, which led to silenced expression.

RELATED: Exploratory Analysis Suggests Benefit With Regorafenib in GIST

Results showed that among patients with SDH­-mutant tumors, approximately 30% presented with metastases, while 40% of those with SDHC-epimutant tumors presented with metastases.

Of note, researchers found that SHD-deficient tumors occurred only in the stomach and were indolent.                                       

Reference

  1. Boikos SA, Pappo AS, Killian K, et al. Molecular subtypes of KIT/PDGFRA wild-type gastrointestinal stromal tumors: A report from the National Institutes of Health [published online ahead of print March 24, 2016]. JAMA Oncol. doi: 10.1001/jamaoncol.2016.0256.

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