Germline Variants in Adult Patients With -Mutant Gastrointestinal Stromal Tumor.

Background: SDH- gastrointestinal stromal tumors (GIST) account for 20-40% of all KIT/PDGFRA-negative GIST and are due to mutations in one of the four -complex subunits, with mutations as the most frequent. Here we sought to evaluate the presence and prevalence of variants in the germline lineage in a population of - GIST.

Methods: Germline status was assessed by Sanger sequencing on a series of 14 patients with gastric - GIST.

Results: All patients carried a germline pathogenic variant, ranging from truncating, missense, or splicing variants. The second hit was the loss of the wild-type allele or an additional somatic mutation. One-third of the patients were over 50 years old. GIST was the only disease presentation in all cases except one, with no personal or familial cancer history. Seven metastatic cases received a multimodal treatment integrating surgery, loco-regional and medical therapy. The mean follow-up time was of 10 years, confirming the indolent clinical course of the disease.

Conclusion: germline variants are highly frequent in SDHA- GIST, and the disease may occur also in older adulthood. Genetic testing and surveillance of -mutation carriers and relatives should be performed.