Synapse - Clinical sequencing defines the genomic landscape of metastatic colorectal cancer

Clinical sequencing defines the genomic landscape of metastatic colorectal cancer Journal Article

Authors:	Yaeger, R.; Chatila, W. K.; Lipsyc, M. D.; Hechtman, J. F.; Cercek, A.; Sanchez-Vega, F.; Jayakumaran, G.; Middha, S.; Zehir, A.; Donoghue, M. T. A.; You, D.; Viale, A.; Kemeny, N.; Segal, N. H.; Stadler, Z. K.; Varghese, A. M.; Kundra, R.; Gao, J.; Syed, A.; Hyman, D. M.; Vakiani, E.; Rosen, N.; Taylor, B. S.; Ladanyi, M.; Berger, M. F.; Solit, D. B.; Shia, J.; Saltz, L.; Schultz, N.
Article Title:	Clinical sequencing defines the genomic landscape of metastatic colorectal cancer
Abstract:	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.
Keywords:	mutation; microsatellite instability; colon; reveals; domain; inhibition; trials; primary tumor location; braf mutants
Journal Title:	Cancer Cell
Volume:	33
Issue:	1
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2018-01-08
Start Page:	125
End Page:	136.e3
Language:	English
ACCESSION:	WOS:000419465500013
DOI:	10.1016/j.ccell.2017.12.004
PROVIDER:	wos
PMCID:	PMC5765991
PUBMED:	29316426
Notes:	Article -- Source: Wos