Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing

被引：140

作者：

Wong, Swee Seong ^{[1
]}

Kim, Kyoung-Mee ^{[2
]}

Ting, Jason C. ^{[1
]}

Yu, Kun ^{[1
]}

Fu, Jake ^{[3
]}

Liu, Shawn ^{[4
]}

Cristescu, Razvan ^{[5
]}

Nebozhyn, Michael ^{[5
]}

Gong, Lara ^{[4
]}

Yue, Yong Gang ^{[1
]}

Wang, Jian ^{[1
]}

Chen Ronghua ^{[5
]}

Loboda, Andrey ^{[5
]}

Hardwick, James ^{[5
]}

Liu, Xiaoqiao ^{[5
]}

Dai, Hongyue ^{[5
]}

Jin, Jason Gang ^{[3
]}

Ye, Xiang S. ^{[1
]}

Kang, So Young ^{[2
]}

Do, In Gu ^{[2
]}

Park, Joon Oh ^{[6
]}

Sohn, Tae Sung ^{[7
]}

Reinhard, Christoph ^{[1
]}

Lee, Jeeyun

Kim, Sung ^{[7
]}

Aggarwal, Amit ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

[2] Sungkyunkwan Univ, Dept Pathol & Translat Genom, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea

[3] Shanghai Biocorp, Shanghai 201203, Peoples R China

[4] BGI Techsolut, Hong Kong, Hong Kong, Peoples R China

[5] Merck Sharp & Dohme Ltd, Merck Res Labs, Boston, MA 02115 USA

[6] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Seoul 135710, South Korea

[7] Sungkyunkwan Univ, Dept Surg, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

MICROSATELLITE INSTABILITY; MISSENSE MUTATIONS; MITOCHONDRIAL-DNA; SOMATIC MUTATIONS; HUMAN CANCERS; TUMOR; GROWTH; EXOME; POPULATION; CATENIN;

D O I：

10.1038/ncomms6477

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. Here we perform whole-genome sequencing of 49 GCs with diffuse (N = 31) and intestinal (N = 18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCp[A/T] nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared with intestinal subtype. We further divide the diffuse subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signalling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC.

引用

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