# Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma

Source: https://onco.cc/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/  
OnCo record `paper-philip-kras-wild-type-pancreatic-ccr-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Clinical Cancer Research
- Year: 2022
- DOI: 10.1158/1078-0432.CCR-21-3581
- Authors: Philip PA, Azar I, Xiu J, et al.
- 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.
- What it means: 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.

## Sources

- Philip et al., Clin Cancer Res 2022: KRAS wild-type tumours among 2,483 pancreatic adenocarcinomas: https://doi.org/10.1158/1078-0432.CCR-21-3581
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35302596/

## Connected records

- cancers: [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma](https://onco.cc/cancers/msi-high-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- targets: [ALK](https://onco.cc/targets/alk/), [BRAF](https://onco.cc/targets/braf/), [FGFR2](https://onco.cc/targets/fgfr2/), [HER2](https://onco.cc/targets/her2/), [KRAS](https://onco.cc/targets/kras/), [MET](https://onco.cc/targets/met/), [Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)](https://onco.cc/targets/mmr/), [NRG1](https://onco.cc/targets/nrg1/), [NTRK](https://onco.cc/targets/ntrk/), [RET](https://onco.cc/targets/ret/), [TP53](https://onco.cc/targets/tp53/)
- companies: [Caris Life Sciences](https://onco.cc/companies/caris/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/), [Wild-type (WT)](https://onco.cc/terms/wild-type/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)
- drugs: [MI Cancer Seek](https://onco.cc/drugs/caris-mi-cancer-seek/)
- biomarkers: [ALK fusion (ALK-positive)](https://onco.cc/biomarkers/alk-fusion/), [NTRK1/2/3 gene fusion](https://onco.cc/biomarkers/ntrk-fusion/), [TMB-high (tumour mutational burden >= 10 mutations per megabase)](https://onco.cc/biomarkers/tmb-high/)

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