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The left-right split is a convenient line but the bowel is a gradient. Mutation rates change continuously from caecum to rectum, and the sigmoid-rectal region and the transverse colon do not fit the convention.
Mutation prevalence and overall survival were compared by side and by precise tumour location in 1,876 patients with colorectal cancer, with consensus molecular subtype compared in a separate cohort of 608. Mutation prevalence differed by side and location for TP53, KRAS, BRAF V600, PIK3CA, SMAD4, CTNNB1, GNAS and PTEN, and substantial variation remained within each side. Within right-sided tumours, RAS mutations fell from 70% in the caecum to 43% at the hepatic flexure, while BRAF V600 mutations rose from 10% to 22% between the same locations. Within left-sided tumours, the sigmoid and rectal region had more TP53 mutations and less PIK3CA, BRAF and CTNNB1 mutation and less microsatellite instability than other left-sided locations. Despite this, a left-right division preceding the transverse colon maximised prognostic differences, and transverse colon tumours clustered with left-sided tumours by mutation profile. Consensus molecular subtype profiles showed a decline in CMS1 and CMS3 and a rise in CMS2 moving distally.
It is the caution attached to the sidedness rule: a tumour at the hepatic flexure and one at the caecum are both called right-sided and are not the same disease.
Shares CTNNB1, Sidedness (left vs right colon), SMAD4, PIK3CA / PI3K-alpha.
Shares SMAD4, PIK3CA / PI3K-alpha, MD Anderson Cancer Center, TP53.
Shares PTEN, PIK3CA / PI3K-alpha, TP53.
Shares SMAD4, Clinical Cancer Research, PIK3CA / PI3K-alpha, TP53.