Molecular subtypes characterize appendiceal adenocarcinoma genomic evolution and disease behavior

摘要: Appendiceal adenocarcinoma (AC) are rare gastrointestinal tumors that exhibit a heterogeneous spectrum of tumor histology and differentiation patterns. Personalized AC treatments are limited by the lack of robust histopathological or genomic predictors of disease behavior. We utilized the MSK IMPACT sequencing panel to profile genomic signature patterns in somatic mutations, copy number alterations, and germline mutations in a large curated dataset of patients with AC. We evaluated co-occurrence and clonality patterns between frequently altered genes in AC (RAS, GNAS, TP53) to establish five molecular subtypes of mucinous appendiceal adenocarcinoma (MAAP): RAS mutated-only, GNAS mutated, TP53 & KRAS mutated, TP53 mutated-only, and none (all wild-type). In multivariable Cox regression models, patients with RAS mutated-only tumors exhibit a nearly non-lethal disease course compared to …