PT  - JOURNAL ARTICLE
AU  - Sebastian Lunke
AU  - Belinda Lee
AU  - Sevastjan Kranz
AU  - Peter Gibbs
AU  - Paul Waring
AU  - Michael Christie
TI  - Intratumorous heterogeneity for RAS mutations in a treatment-naïve colorectal tumour
AID  - 10.1136/jclinpath-2017-204327
DP  - 2017 Mar 17
TA  - Journal of Clinical Pathology
PG  - jclinpath-2017-204327
4099  - http://jcp.bmj.com/content/early/2017/03/17/jclinpath-2017-204327.short
4100  - http://jcp.bmj.com/content/early/2017/03/17/jclinpath-2017-204327.full
AB  - Activating mutations in KRAS and NRAS genes 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.