Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer

被引：711

作者：

Yaeger, Rona ^{[1
]}

Chatila, Walid K. ^{[2
]}

Lipsyc, Marla D. ^{[1
]}

Hechtman, Jaclyn F. ^{[3
]}

Cercek, Andrea ^{[1
]}

Sanchez-Vega, Francisco ^{[2
]}

Jayakumaran, Gowtham ^{[3
]}

Middha, Sumit ^{[3
]}

Zehir, Ahmet ^{[3
]}

Donoghue, Mark T. A.

You, Daoqi

Viale, Agnes

Kemeny, Nancy ^{[1
]}

Segal, Neil H. ^{[1
]}

Stadler, Zsofia K. ^{[1
]}

Varghese, Anna M. ^{[1
]}

Kundra, Ritika ^{[2
]}

Gao, Jianjiong ^{[2
]}

Syed, Aijazuddin ^{[3
]}

Hyman, David M. ^{[1
]}

Vakiani, Efsevia ^{[3
]}

Rosen, Neal ^{[1
]}

Taylor, Barry S. ^{[2
,4
,5
,6
]}

Ladanyi, Marc ^{[3
,6
]}

Berger, Michael F. ^{[2
,3
,6
]}

Solit, David B. ^{[1
,2
,6
]}

Shia, Jinru ^{[3
]}

Saltz, Leonard ^{[1
]}

Schultz, Nikolaus ^{[2
,4
,5
,6
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Marie Josee & Henry R Kravis Ctr Mol Oncol, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[4] Mem Sloan Kettering Canc Ctr, Dept Epidemiol, New York, NY 10065 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10065 USA

[6] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

来源：

CANCER CELL | 2018年 / 33卷 / 01期

关键词：

MICROSATELLITE INSTABILITY; BRAF MUTANTS; MUTATION; DOMAIN; COLON;

D O I：

10.1016/j.ccell.2017.12.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：125 / +

页数：15

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