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Are all RAS mutations the same? Coexisting KRAS and NRAS mutations in a caecal adenocarcinoma and contiguous

N N Vagaja1, J Parry1, D McCallum1

  • 1Anatomical Pathology, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia Anatomical Pathology, PathWest Laboratory Medicine, Fiona Stanley Hospital Network, Murdoch, Western Australia, Australia.

Journal of Clinical Pathology
|May 1, 2015
PubMed

Insights

This study reports a rare case of colorectal cancer with simultaneous KRAS and NRAS mutations, originating from a shared precursor. This finding may offer clinical insights into distinct RAS pathway functions in colon cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and neuroblastoma RAS viral oncogene homologue (NRAS) are linked to resistance against anti-epidermal growth factor receptor therapies in colorectal cancer patients.
  • RAS pathway mutations are critical drivers in various cancers, including colorectal cancer, influencing therapeutic responses.

Observation:

  • A case of caecal adenocarcinoma is presented, exhibiting concurrent KRAS c.35G>T (G12V) and NRAS c.34G>A (G12S) mutations.
  • The adenocarcinoma developed from a high-grade tubulovillous adenoma that harbored the same KRAS and NRAS mutations, indicating a common clonal origin.

Findings:

  • While KRAS mutations are prevalent in colorectal cancer, NRAS mutations are infrequent.
  • The simultaneous occurrence of multiple RAS mutations, as observed in this case, is previously undocumented in colorectal cancer.
  • This case provides potential clinical evidence supporting recent hypotheses that KRAS and NRAS may regulate distinct biological processes within the colon.

Implications:

  • Understanding the specific and potentially divergent roles of different RAS family members and their mutants in colon carcinogenesis is crucial.
  • Further characterization of RAS pathway signaling is essential for developing more targeted and effective RAS-targeting therapeutics for colorectal cancer.
Keywords:
COLORECTAL CANCERMOLECULAR BIOLOGYMOLECULAR PATHOLOGY

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