| Literature DB >> 29316426 |
Rona Yaeger1, Walid K Chatila2, Marla D Lipsyc1, Jaclyn F Hechtman3, Andrea Cercek1, Francisco Sanchez-Vega2, Gowtham Jayakumaran3, Sumit Middha3, Ahmet Zehir3, Mark T A Donoghue2, Daoqi You2, Agnes Viale2, Nancy Kemeny1, Neil H Segal1, Zsofia K Stadler1, Anna M Varghese1, Ritika Kundra2, Jianjiong Gao2, Aijazuddin Syed3, David M Hyman1, Efsevia Vakiani3, Neal Rosen1, Barry S Taylor4, Marc Ladanyi5, Michael F Berger6, David B Solit7, Jinru Shia3, Leonard Saltz1, Nikolaus Schultz8.
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.Entities:
Keywords: APC; CTNNB1; colorectal cancer; integrative genomics analysis; intronic alterations; location; prognosis
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Year: 2018 PMID： 29316426 PMCID： PMC5765991 DOI： 10.1016/j.ccell.2017.12.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743