MSK GIST Germline Study (2022)

Overview

Institutional cohort from Memorial Sloan Kettering Cancer Center profiling gastrointestinal stromal tumor (GIST) patients for germline pathogenic/likely pathogenic (P/LP) variants. The study includes 103 patients who consented to germline analysis (April 2015–June 2021) and an expanded de-identified cohort of 499 tumor-normal pairs sequenced by MSK-IMPACT. The dataset is publicly available on cBioPortal as gist_msk_2022.

Composition

  • 103 consented GIST patients with paired germline sequencing; 499 tumor-normal pairs in the broader cohort.
  • Sequenced with MSK-IMPACT (341, 410, or 505 gene panels).
  • Key clinical fields: age at diagnosis, syndromic history (NF1, SDH-related paraganglioma/pheochromocytoma), KIT/PDGFRA mutation status.

Assays / panels (linked)

  • MSK-IMPACT — targeted tumor-normal sequencing (341/410/505 gene panels)

Papers using this cohort

  • PMID:36593350 — Mandelker et al., npj Precision Oncology 2023. Germline testing in GIST reveals high frequency of non-syndromic pathogenic variants.

Notable findings derived from this cohort

  • 69% (24/35) of KIT/PDGFRA-wildtype GIST patients harbored germline P/LP variants in GIST-associated genes (SDHA, SDHB, SDHC, NF1, KIT), and 63% of those had no personal or family history of syndromic features PMID:36593350.
  • 23% (24/103) of unselected GIST patients had a germline P/LP variant; patients with germline variants had younger median age-of-onset (39.5 vs 52 years, p=0.01) and higher rates of metastatic disease (50% vs 20%, p=0.01) PMID:36593350.
  • ESMO-recommended VAF thresholds (>30% for SNVs, >20% for indels) correctly distinguished all germline from somatic P/LP variants in the 499-patient tumor-only cohort PMID:36593350.
  • SDHB and BRCA2 variants in tumor-only sequencing were almost exclusively germline in origin (10/11 and 4/4 respectively), supporting reflex germline testing PMID:36593350.

Sources

  • cBioPortal study: gist_msk_2022
  • Associated publication: PMID:36593350

This page was processed by crosslinker on 2026-05-05.