Review of Genomic Testing and SDH Deficiency in Gastrointestinal Stromal Tumors: Getting to the GIST
Genomic testing is essential for accurate diagnosis, treatment planning, and surveillance of gastrointestinal stromal tumors, particularly for SDH‑deficient cases.
Gastrointestinal Stromal Tumors (GISTs) have seen significant advancements in their diagnosis and management, driven by targeted therapeutic development and molecular testing. The identification of mutations in genes such as KIT and PDGFRA has transformed treatment approaches, particularly through targeted therapies like imatinib, which have improved patient outcomes. This review explores the critical role of genomic testing in GIST, highlighting its importance in accurate diagnosis, treatment planning, and long‑term surveillance for KIT/PDGFRA negative, SDH‑deficient GISTs. SDH‑deficient GISTs arise from mutations or epigenetic changes affecting the succinate dehydrogenase complex. The complexity of SDH‑deficient GISTs, including their association with hereditary syndromes such as Hereditary Paraganglioma‑Pheochromocytoma and/or hypermethylation of the SDHC promoter, underscores the need for comprehensive germline testing. Despite the availability of guidelines, variability exists in genomic testing recommendations across different regions, necessitating a unified approach. This review proposes a simplified algorithm for the genomic workup of GIST, and suggests all individuals with SDH‑deficient GIST, regardless of germline testing result, require monitoring for additional SDHx‑related tumors, given the lack of widely available methylation and full gene SDHA analysis.
Genomic testing allows clinicians to identify actionable mutations, guiding targeted therapy choices and surveillance strategies, which can improve survival and reduce unnecessary interventions for patients with GIST.
Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.
Kapcsolódó jelek
- A case report of advanced small intestinal stromal tumor with KIT gene mutation and BRCA2 deletion after multi-line treatments
- Molecular Tailored Therapeutic Options for Advanced Gastrointestinal Stromal Tumors (GISTs): Current Practice and Future Perspectives
- Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach
- UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST)
- Phase II Trial of Ponatinib in Patients with Metastatic Gastrointestinal Stromal Tumor following Failure or Intolerance of Prior Therapy with Imatinib (POETIG Trial)