Intratumorous heterogeneity for RAS mutations in a treatment-naïve colorectal tumour.
Activating mutations inKRASandNRASgenes in patients with colorectal cancer (CRC) are associated with a lack of response to treatment with anti-epidermal growth factor receptor (EGFR) therapies. Mutations in these genes are thought to be mutually exclusive, however reports have described CRCs with two activating rat sarcoma (RAS) mutations. This has fuelled discussion about whether these mutations are the result of intratumorous heterogeneity, or if they are co-occurring in the same cancer cell clone. We present a case of a colorectal tumour with three RAS mutations detected during routine diagnostic testing. Further detailed analysis with laser capture microdissection and next generation sequencing excluded the possibility of all three mutations being present in the same clone, presenting the highest resolution evidence of intratumorous heterogeneity of RAS mutations to date.
Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
Sebastian
http://orcid.org/0000-0002-7168-0723
S
Lunke
Colorectal Translational Oncology Group, Walter and Eliza Hall Institute, Parkville, Victoria, Australia.
Belinda
B
Lee
Department of Pathology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Sevastjan
S
Kranz
Colorectal Translational Oncology Group, Walter and Eliza Hall Institute, Parkville, Victoria, Australia.|Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Peter
P
Gibbs
Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
Paul
P
Waring
Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.|Colorectal Translational Oncology Group, Walter and Eliza Hall Institute, Parkville, Victoria, Australia.|Department of Pathology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Michael
M
Christie
D000230:Adenocarcinoma / Q000235:genetics*; D000369:Aged, 80 and over; D005787:Gene Frequency; D052138:Genes, Neoplasm / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D009154:Mutation / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics*
CANCER GENETICS; COLORECTAL CANCER; DIAGNOSTICS; HISTOPATHOLOGY; TUMOUR MARKERS