Clinical sequencing defines the genomic landscape of metastatic colorectal cancer
By R. Yaeger, W. Chatila, Marla D Lipsyc, J. Hechtman, A. Cercek, F. Sánchez-Vega, G. Jayakumaran, Sumit Middha, A. Zehir, M. Donoghue and 19 more. Cancer Cell, 2018
775 citations recorded by the source corpus.
Summary Metastatic colorectal cancers (mCRCs) are clinically heterogeneous, but the genomic basis of this variability remains poorly understood. We performed prospective targeted sequencing of 1134 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 to 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.
Subfields: Cancer Research, Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/168f5646d870d017b062404c10f276e8bf0f82f3
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