Molecular Features of Gastrointestinal Stromal Tumors: A Single Referral Cancer Center Experience

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract. They frequently harbor mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT) (70-80%) and platelet-derived growth factor receptor alpha (PDGFRA) (10-15%) genes, responding effectively to tyrosine kinase inhibitors (TKIs). Accurate genotyping is crucial for diagnosis and therapeutic management. This study reports a decade-long experience, detailing the epidemiological, pathological, and molecular characteristics of GISTs in a single-center cohort.

Twenty-nine patients diagnosed with GIST (stomach, small bowel, colon, and peritoneum) at IRCCS CROB, Italy, between 2012 and 2021 were enrolled. Molecular analysis was performed using Sanger sequencing and Next-Generation Sequencing (NGS).

Twenty-three patients (85%) harbored KIT mutations, while four (15%) had PDGFRA mutations. Among KIT-mutated cases, five (22%) presented the p.Ala502_Tyr503dup duplication in exon 9. Elevated Ki-67 and a mitotic index of 3-7/50 high-power field (HPF) were associated with high recurrence risk. Eighteen patients (78%) exhibited mutations in exon 11: 8 (44%) were point mutations, 5 (28%) deletions, and 5 (28%) complex deletions. Point mutations at codons 557, 560, and 603 correlated with high recurrence risk, whereas mutations at codons 559 and 599 linked to low-risk disease. Most deletions and complex deletions showed high recurrence risk and Ki-67 >10%. PDGFRA mutations were located in exon 18 (2 complex deletions, 2 point mutations including p.D842V); three of these cases showed low-to-moderate recurrence risk (Ki-67 ≤8%).

This study characterizes the clinicopathological and molecular profiles of 29 Caucasian GIST patients, reinforcing the critical role of molecular stratification in clinical practice.