Are all RAS mutations the same? Coexisting KRAS and NRAS mutations in a caecal adenocarcinoma and contiguous tubulovillous adenoma.
Mutations of the human Kirsten rat sarcoma viral oncogene homologue (KRAS) and the highly homologous human neuroblastoma RAS viral oncogene homologue (NRAS) are associated with resistance to antiepidermal growth factor receptor therapies in patients with colorectal cancer. In this report, we describe a caecal adenocarcinoma that contains both KRAS c.35G>T (G12V) and NRAS c.34G>A (G12S) mutations. The adenocarcinoma arises from a contiguous high-grade tubulovillous adenoma, which also carries the identical KRAS and NRAS mutations, supporting their common origin. While KRAS mutations are common in colorectal cancers, NRAS mutations are relatively rare and the coexistence of multiple RAS mutations is not documented, presumably reflecting similar functions of wild-type and mutant forms of RAS. Recent experimental evidence has suggested that KRAS and NRAS may in fact mediate distinct biological processes in the colon, and this unusual case potentially illustrates the hypothesis clinically. Characterisation of the diverse and divergent functions of RAS family members and mutant forms of RAS in the colon form important considerations for the development of RAS-targeting therapeutics.
Anatomical Pathology, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia Anatomical Pathology, PathWest Laboratory Medicine, Fiona Stanley Hospital Network, Murdoch, Western Australia, Australia.
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Vagaja
Anatomical Pathology, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia Anatomical Pathology, PathWest Laboratory Medicine, Fiona Stanley Hospital Network, Murdoch, Western Australia, Australia.
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Parry
Anatomical Pathology, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia Anatomical Pathology, PathWest Laboratory Medicine, Fiona Stanley Hospital Network, Murdoch, Western Australia, Australia.
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McCallum
Anatomical Pathology, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia Anatomical Pathology, PathWest Laboratory Medicine, Fiona Stanley Hospital Network, Murdoch, Western Australia, Australia.
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Thomas
Anatomical Pathology, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia Anatomical Pathology, PathWest Laboratory Medicine, Fiona Stanley Hospital Network, Murdoch, Western Australia, Australia.
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Bentel
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018253:Adenoma, Villous / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D002430:Cecal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003082:Colectomy; D004252:DNA Mutational Analysis; D020558:GTP Phosphohydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D060787:Neoplasm Grading; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
COLORECTAL CANCER; MOLECULAR BIOLOGY; MOLECULAR PATHOLOGY