{"entity":{"id":"paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018","kind":"paper","name":"Clinical sequencing defines the genomic landscape of metastatic colorectal cancer","aka":[],"tldr":"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.","summary":"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.\n\nDeposited 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).","asOf":"2026-09-24","links":[{"label":"Yaeger et al., Cancer Cell 2018: prospective targeted sequencing of 1,134 colorectal cancers (MSK)","url":"https://doi.org/10.1016/j.ccell.2017.12.004"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29316426/"},{"label":"cBioPortal study crc_msk_2017 (MSK, Cancer Cell 2018; 1,134 MSK-IMPACT samples from patients with metastatic disease, 601 primaries and 533 metastases)","url":"https://www.cbioportal.org/study/summary?id=crc_msk_2017"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["cgp","ngs-bioinformatics-software"],"targets":["apc","ctnnb1","kras","braf","pik3ca","rnf43","smad4"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["wnt","ras-mapk","colorectal-cancer-signalling"],"terms":["sidedness","wild-type","ngs"],"trials":[],"people":["rona-yaeger","andrea-cercek"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2018,"doi":"10.1016/j.ccell.2017.12.004","pmid":"29316426","authors":"Yaeger R, Chatila WK, Lipsyc MD, et al.","paperType":"observational","findings":["Oncogenic WNT alterations in 96% of cancers once intronic APC splice events and large in-frame CTNNB1 deletions are counted.","Right-sided microsatellite-stable tumours enriched for KRAS, BRAF, PIK3CA, AKT1, RNF43 and SMAD4 alterations and shorter survival.","Left-sided tumours often lack a mitogenic driver but express more mitogenic ligand."],"whatItMeans":"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.","caveats":["A targeted panel, so genes off MSK-IMPACT read zero.","A referral population enriched for metastatic disease, which lowers the measured microsatellite instability rate.","Ligand expression was measured in a subset."],"changedPractice":false,"participants":1134},"route":"/key-papers/paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"ngs-bioinformatics-software","kind":"technology","name":"Clinical NGS bioinformatics and variant interpretation","route":"/technologies/ngs-bioinformatics-software/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"}],"target":[{"id":"apc","kind":"target","name":"APC","route":"/targets/apc/"},{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"ctnnb1","kind":"target","name":"CTNNB1","route":"/targets/ctnnb1/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"},{"id":"rnf43","kind":"target","name":"RNF43","route":"/targets/rnf43/"},{"id":"smad4","kind":"target","name":"SMAD4","route":"/targets/smad4/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"colorectal-cancer-signalling","kind":"pathway","name":"Colorectal cancer (KEGG map)","route":"/pathways/colorectal-cancer-signalling/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"term":[{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"}],"person":[{"id":"andrea-cercek","kind":"person","name":"Andrea Cercek","route":"/people/andrea-cercek/"},{"id":"rona-yaeger","kind":"person","name":"Rona Yaeger","route":"/people/rona-yaeger/"}],"journal":[{"id":"cancer-cell","kind":"journal","name":"Cancer Cell","route":"/journals/cancer-cell/"}]}}