Comparative mutational analysis of biliary tract cancers.

Abstract

e16164 Background: Traditional classifications of tumors have utilized tissue of origin and histologic types. These categories have been refined with comprehensive molecular characterizations across large numbers of tumors. We hereby aimed to identify the similarities and differences of mutational profiles among the cancers along biliary tract, and investigate their prognostic effects. Methods: Mutation and clinical data from 99 BTC patients who received surgical resection (gallbladder cancer [GBC], n=42; cholangiocarcinoma [CCA], n=57) were analyzed. Capture-based targeted deep sequencing was performed using a 520-gene panel, spanning 1.64 Mb of the human genome (Burning Rock Biotech). Results: The mutational frequencies of TP53, BRCA1/2, ATM, and PI3K, WNT, HRR, and cell cycle pathway, gradually decreased with the order of the anatomical position (GBC, dCCA, pCCA, iCCA-large duct, and iCCA-small duct), while the changing trend of BRAF mutational frequency was the opposite (Table). In addition, CCND1/E1 and APC mutations were enriched in metastatic BTCs. As for prognostic effect, mutations of BRAF, TGFBR1/2, ARID1A, and MMR pathway were associated with shorter OS, and these association remained significant after adjustment for tissue of origin, TNM stage, histological grade, surgical margin, and serum CEA level. Conclusions: The differentially mutated genes among the cancers along biliary tract may indicate the potential mechanism of tumor development in different anatomic locations. Deeper understanding of the prognosis-related mutational events might change the postoperative management of BTC by enabling risk stratification, ACT monitoring, and early relapse detection. Mutational rate of the differentially mutated genes among the cancers along biliary tract.[Table: see text]