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Sequencing 1,134 bowel cancers in the clinic rather than in a research study showed that essentially every one of them has the WNT growth signal switched on, and that right-sided and left-sided tumours reach that state by different routes.
Prospective targeted sequencing of 1,134 colorectal cancers identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, taking oncogenic WNT pathway alterations to 96% of colorectal cancers. Right-sided primary site in microsatellite-stable metastatic disease was associated with shorter survival, older age at diagnosis, more mutations and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43 and SMAD4 compared with left-sided primaries. Left-sided tumours frequently had no identifiable genetic alteration in mitogenic signalling but exhibited higher mitogenic ligand expression. The authors concluded that right- and left-sided microsatellite-stable colorectal cancers follow different routes to tumourigenesis.
Deposited as crc_msk_2017 on cBioPortal (1,134 MSK-IMPACT samples; 601 primaries and 533 metastases; 1,120 with a recorded side, 341 right and 779 left).
It turned sidedness from an epidemiological curiosity into a mechanistic statement, and it is the reason a wild-type mitogenic report on a left-sided tumour is read as ligand dependence rather than as an absence.
Shares CTNNB1, Sidedness (left vs right colon), SMAD4, PIK3CA / PI3K-alpha.
Shares RNF43, Wild-type (WT), CTNNB1, Cancer Cell.
Shares RNF43, Wnt / β-catenin, BRAF, RAS / RAF / MEK / ERK (MAPK).
Shares Wild-type (WT), Next-generation sequencing (NGS), BRAF, RAS / RAF / MEK / ERK (MAPK).
Shares APC, SMAD4, Next-generation sequencing (NGS), Wnt / β-catenin.
Shares RNF43, Wnt / β-catenin, BRAF, RAS / RAF / MEK / ERK (MAPK).
Shares APC, SMAD4, Colorectal cancer (KEGG map), KRAS.
Shares Wild-type (WT), Sidedness (left vs right colon), BRAF, KRAS.