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Updated: Jan 14, 2026

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
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KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts

Emerik Osterlund1,2, Ari Ristimäki3,4, Luís Nunes5,6

  • 1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. emerik.osterlund@igp.uu.se.

BJC Reports
|October 21, 2025
PubMed
Abstract

Insights

KRAS and NRAS mutations drive metastatic colorectal cancer (mCRC). This study found no significant clinical differences between KRAS and NRAS mutations, though specific KRAS mutations like KRAS-G12S showed distinct metastatic patterns and survival outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • KRAS and NRAS mutations are key drivers in metastatic colorectal cancer (mCRC).
  • Understanding the frequencies and clinical impact of these mutations is crucial for treatment strategies.
  • Real-world data provides valuable insights into patient populations.

Purpose of the Study:

  • To determine the frequencies of KRAS and NRAS mutations in mCRC.
  • To compare the clinical characteristics, treatments, and outcomes associated with different KRAS and NRAS mutations.
  • To identify specific mutation subtypes that may influence patient prognosis.

Main Methods:

  • Combined analysis of three Nordic cohorts comprising 2649 mCRC patients.
  • Molecular characterization for KRAS, NRAS, and BRAF-V600E hotspot mutations.
  • Statistical analysis of clinical characteristics, treatment data, and overall survival (OS).

Main Results:

  • KRAS mutations (mt) were found in 49% and NRAS mutations in 4% of patients.
  • No significant clinical differences were observed between KRASmt and NRASmt.
  • BRAF-V600Emt had the shortest OS (9.2 months), while RAS and BRAF wild-type (wt) had the longest (28.3 months).
  • KRAS-G12S mutations were associated with more distant lymph node metastases and shorter OS compared to other common KRAS mutations.

Conclusions:

  • KRAS mutations occur in 49% and NRAS mutations in 4% of mCRC cases.
  • Clinically relevant differences between RAS mutations were not identified in this study.
  • KRAS mutations represent a significant subgroup in mCRC, with potential for improved outcomes with emerging therapies.

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