What question did this study set out to answer?

To characterize the clinicopathological features, clinical outcomes, and underlying molecular alterations in KRAS wild-type pancreatic ductal adenocarcinomas and their precursor lesions.

May 2, 2025The Journal of PathologyOpen Access

Clinicopathological and molecular characterization of KRAS wild‐type pancreatic ductal adenocarcinomas reveals precursor lesions with oncogenic mutations and fusions in RAS pathway genes

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Authors

KTKan ToriyamaAichi Cancer Center KMKatsuhiro MasagoAichi Cancer Center NSNorio ShibataNagoya Institute of Technology

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Implication

Cohort study reveals frequent actionable RAS pathway alterations in KRAS wild-type pancreatic cancer, indicating early alternative drivers initiate tumorigenesis.

Key Points

To characterize the clinicopathological features, clinical outcomes, and underlying molecular alterations in KRAS wild-type pancreatic ductal adenocarcinomas and their precursor lesions.
Evaluated clinicopathological characteristics and survival outcomes in 75 patients with KRAS wild-type pancreatic ductal adenocarcinoma.
Performed targeted DNA sequencing, whole-exome sequencing, and targeted RNA sequencing on tumors from 40 patients.
Analyzed precancerous lesions across 13 pancreatectomy specimens from patients with KRAS wild-type disease.
Patients with metastatic KRAS wild-type disease presented at a significantly younger median age than those with mutated KRAS (59.5 vs 67.0 years, p < 0.000055), though KRAS wild-type status was not independently prognostic for metastatic survival.
RAS pathway genes were mutated or rearranged in 46% (16/35) of tested tumors, and actionable alterations were significantly enriched in nontubular carcinomas compared with tubular adenocarcinomas (67% [6/9] vs 16% [5/31], p = 0.007).
Precursor lesions, including three pancreatic intraepithelial neoplasias and two intraductal papillary mucinous neoplasms, harbored driver mutations in BRAF and AKT1 along with oncogenic ALK and BRAF fusions.

Cite This Study

Toriyama et al. (2025) studied this question.

synapsesocial.com/papers/6a1d2b2568a6eca4522f4be6 https://doi.org/10.1002/path.6432

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Implication

Cohort study reveals frequent actionable RAS pathway alterations in KRAS wild-type pancreatic cancer, indicating early alternative drivers initiate tumorigenesis.

Clinicopathological and molecular characterization of KRAS wild‐type pancreatic ductal adenocarcinomas reveals precursor lesions with oncogenic mutations and fusions in RAS pathway genes

Discussion

Member takes

Implication

Key Points

Cite This Study

Clinicopathological and molecular characterization of KRAS wild‐type pancreatic ductal adenocarcinomas reveals precursor lesions with oncogenic mutations and fusions in RAS pathway genes

Discussion

Member takes

Implication

Key Points

Cite This Study

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