Gastrointestinal stromal tumors (GISTs) are usually caused by somatic mutations, but there are rare germline variants that predispose patients to the development of one or, more commonly, multiple GISTs. We present 2 cases of multifocal GISTs related to previously unreported germline variants. The first case is a 28-year-old female who developed multiple gastric GISTs with widespread abdominal metastases that were resistant to imatinib. Assessment by Medical Genetics identified a germline SDHB splice site mutation (NM_003000.3, c.286 + 2T > G, p.?). The second case is a 64-year-old male who presented with multiple gastric tumors that were resistant to imatinib. Next-generation sequencing revealed a germline KIT exon 17 mutation (NM_000222.3, c.2459A > T, p.D820V). These cases highlight the diverse clinical presentations of patients with germline variants and raise several important points about the diagnosis and management of these patients, in particular: mutation in the SDH family of genes (somatic or germline) should be suspected in KIT and PDGFRA wild-type tumors; germline testing should be considered in patients with multiple GISTs or those who present with disease at a young age; and somatic next-generation sequencing cannot only help identify optimal therapy in all patients with GISTs but also help guide referral to Medical Genetics for appropriate patients.
Keywords: Gastric cancer; Gastrointestinal stromal tumors; Hereditary cancer syndromes; Next-generation sequencing.
© 2022. Japanese Society of Gastroenterology.