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Among 2,483 pancreatic cancers profiled by one commercial laboratory, the 10.7% without a KRAS mutation more often carried BRAF changes, kinase fusions, microsatellite instability and a high mutation burden, had more immune cells, and lived longer on chemotherapy.
Tumour tissue underwent next-generation DNA and RNA sequencing with MSI and mismatch repair status. Of 2,483 patients, 266 (10.7%) were KRAS wild-type. The most frequently mutated gene in wild-type tumours was TP53 (44.5%), then BRAF (13.0%), with frequent DNA-damage repair (BRCA2, ATM, BAP1, RAD50, FANCE, PALB2), chromatin remodelling and cell-cycle gene alterations. PD-L1 expression did not differ (15.8% versus 17%), but wild-type tumours were more often MSI-high (4.7% versus 0.7%) and TMB-high (4.5% versus 1%) with more CD8 T cells, NK cells and myeloid dendritic cells. Wild-type tumours carried fusions of BRAF (6.6%), FGFR2 (5.2%), ALK (2.6%), RET (1.3%) and NRG1 (1.3%) and amplification of FGF3 (3%), ERBB2 (2.2%), FGFR3 (1.8%), NTRK (1.8%) and MET (1.3%). Real-world data showed a survival advantage for wild-type patients overall and on gemcitabine/nab-paclitaxel or 5-FU/oxaliplatin.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
Shares Wild-type (WT), NRG1, Clinical Cancer Research, KRAS wild-type pancreatic ductal adenocarcinoma.
Shares Wild-type (WT), NRG1, KRAS wild-type pancreatic ductal adenocarcinoma, Receptor tyrosine kinase activation.
Shares TMB-high (tumour mutational burden >= 10 mutations per megabase), NTRK1/2/3 gene fusion, NTRK, Clinical Cancer Research.
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 Caris Life Sciences, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares TMB-high (tumour mutational burden >= 10 mutations per megabase), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Wild-type (WT), NRG1, KRAS wild-type pancreatic ductal adenocarcinoma, Receptor tyrosine kinase activation.