{"entity":{"id":"paper-philip-kras-wild-type-pancreatic-ccr-2022","kind":"paper","name":"Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"Philip et al., Clin Cancer Res 2022: KRAS wild-type tumours among 2,483 pancreatic adenocarcinomas","url":"https://doi.org/10.1158/1078-0432.CCR-21-3581"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35302596/"}],"tags":[],"related":[],"cancers":["pancreatic","kras-wild-type-pdac","msi-high-pdac"],"sections":[],"technologies":["rna-seq"],"targets":["kras","braf","fgfr2","alk","ret","nrg1","her2","ntrk","met","tp53"],"drugs":[],"companies":["caris"],"institutions":[],"pathways":["rtk-activation","ras-mapk"],"terms":["wild-type","msi","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2022,"doi":"10.1158/1078-0432.CCR-21-3581","pmid":"35302596","authors":"Philip PA, Azar I, Xiu J, et al.","paperType":"real-world","findings":["KRAS wild-type 10.7%; TP53 44.5% and BRAF 13.0% within it.","Fusions in wild-type tumours: BRAF 6.6%, FGFR2 5.2%, ALK 2.6%, RET 1.3%, NRG1 1.3%.","MSI-high 4.7% versus 0.7% and TMB-high 4.5% versus 1%; survival advantage for wild-type."],"whatItMeans":"This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.","caveats":["Commercial referral cohort (Caris); survival from real-world records.","Fusion percentages rest on 266 tumours."],"changedPractice":false,"participants":2483},"route":"/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/","neighbours":{"cancer":[{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"msi-high-pdac","kind":"cancer","name":"Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma","route":"/cancers/msi-high-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"fgfr2","kind":"target","name":"FGFR2","route":"/targets/fgfr2/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"},{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"},{"id":"nrg1","kind":"target","name":"NRG1","route":"/targets/nrg1/"},{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"},{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"company":[{"id":"caris","kind":"company","name":"Caris Life Sciences","route":"/companies/caris/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}],"drug":[{"id":"caris-mi-cancer-seek","kind":"drug","name":"MI Cancer Seek","route":"/drugs/caris-mi-cancer-seek/"}],"biomarker":[{"id":"alk-fusion","kind":"biomarker","name":"ALK fusion (ALK-positive)","route":"/biomarkers/alk-fusion/"},{"id":"ntrk-fusion","kind":"biomarker","name":"NTRK1/2/3 gene fusion","route":"/biomarkers/ntrk-fusion/"},{"id":"tmb-high","kind":"biomarker","name":"TMB-high (tumour mutational burden >= 10 mutations per megabase)","route":"/biomarkers/tmb-high/"}]}}