Genome analyses of pancreatic ductal adenocarcinoma: Current status and future perspectives

Abstract

Genome analyses of pancreatic ductal adenocarcinoma (PDAC) have revealed somatic mutations frequently in KRAS, TP53, SMAD4, and CDKN2A, as well as less frequently in ARID1A, ARID2, SMARCA4, KMT2C, KMT2D, KDM6A, RNF43, FAT1, FAT2, FAT3, FAT4, and TGFBR2. The only targetable KRAS mutation, KRAS G12C, has been identified in 2.6% of all KRAS mutations in patients with PDACs. Transcriptome analyses have revealed that PDACs can be classified into the classical type and the basal-like/squamous type, in which the latter is associated with a poorer prognosis than the former. Familial pancreatic cancer accounts for 7% of PDAC cases, and are likely to harbor deleterious germline mutations in APC, ATM, BRCA1, BRCA2, CHEK2, ERCC2, FANCA, FANCC, FANCE, FAT4, KMT2C, MLH1, MSH2, NF1, PALB2, POLE, RNF43, SMAD4, TP53, and TSC2. In the future, genome analyses of some specific cohorts or individuals with detailed clinical information may uncover more useful, clinically-oriented information that can make personalized medicine more efficient.