Loading
Targeted sequencing of 3,594 pancreatic cancers, the largest such series, found KRAS in 88%, a drug-matchable alteration in 17%, BRCA or FANC repair gene changes in 14%, and microsatellite instability or very high mutation burden in only 0.5%.
Targeted genomic profiling of 3,594 pancreatic ductal adenocarcinoma samples from an international cohort covered up to 315 cancer genes and the introns of 28 rearranged genes, with tumour mutation burden over 1.14 megabases (high at 20 or more per megabase) and MSI over 114 loci. KRAS, TP53, CDKN2A and SMAD4 were the most frequently altered genes; KRAS was mutated in 88%. Among KRAS wild-type tumours, actionable MAPK pathway alterations (n = 132; 4%) included gene fusions (51), amplifications (35), missense mutations (30) and deletions (16), mostly in receptor tyrosine kinase, RAS or MAPK genes. Beyond TP53, DNA damage repair alterations (BRCA and FANC) were found in 14%. MSI-high and/or TMB-high phenotypes were detected in 0.5% of 2,563 and 1,021 evaluated. FGF23, CCND2, PIK3CA and FGF6 alterations were commoner in IPMN-associated cancers. Overall 17% carried alterations that might make tumours susceptible to existing agents.
It fixed the working numbers for a comprehensive panel in pancreatic cancer: a hit worth acting on in about one patient in six, most of it in repair genes and the KRAS wild-type minority.
Shares TMB-high (tumour mutational burden >= 10 mutations per megabase), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), SMAD4, CDKN2A.
Shares TMB-high (tumour mutational burden >= 10 mutations per megabase), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma, KRAS wild-type pancreatic ductal adenocarcinoma.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), FoundationOne CDx / Liquid CDx, Next-generation sequencing (NGS), BRCA1 / BRCA2 (HRD).
Shares Anirban Maitra, Gastroenterology, CDKN2A, KRAS.
Shares MSI and mismatch-repair testing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Gastroenterology, SMAD4, TP53, KRAS.
Shares Gastroenterology, SMAD4, CDKN2A, TP53.
Shares Anirban Maitra, SMAD4, CDKN2A, TP53.