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Metastatic colorectal cancers (mCRCs) are clinically heterogeneous, but the genomic basis of this variability remains poorly understood. We performed prospective targeted sequencing of 1,134 CRCs. We identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, increasing oncogenic WNT pathway alterations to 96% of CRCs. Right-sided primary site in microsatellite stable mCRC was associated with shorter survival, older age at diagnosis, increased mutations, and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43, and SMAD4 compared with left-sided primaries. Left-sided tumors frequently had no identifiable genetic alteration in mitogenic signaling, but exhibited higher mitogenic ligand expression. Our results suggest different pathways to tumorigenesis in right- and left-sided microsatellite stable CRC that may underlie clinical differences.
Pubmed ID: 29316426 RIS Download
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Precision oncology knowledge base which contains information about the effects and treatment implications of specific cancer gene alterations. OncoKB contains detailed information about specific alterations in 418 cancer genes. Each variant entry contains biological effect, prevalence, prognostic information, and treatment implications. Information is curated from various sources, such as guidelines from the FDA, ClinicalTrials.gov, and scientific literature by a network of clinical fellows, research fellows, and faculty members at Memorial Sloan Kettering Cancer Center.
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