Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/100653
Title: A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets
Authors: Tao, Jiong
Tan, Iain Beehuat
Deng, Niantao
Goh, Liang-Kee
Wang, Hannah
Das, Kakoli
Zhang, Shenli
Lee, Minghui
Wu, Jeanie
Lim, Kiat Hon
Lei, Zhengdeng
Goh, Glenn
Lim, Qing-Yan
Tan, Angie Lay-Keng
Poh, Dianne Yu Sin
Riahi, Sudep
Bell, Sandra
Linnartz, Ronald
Zhu, Feng
Yeoh, Khay Guan
Toh, Han Chong
Yong, Wei Peng
Cheong, Hyun Cheol
Rha, Sun Young
Boussioutas, Alex
Grabsch, Heike
Tan, Patrick
Shi, Michael M.
Rozen, Steve G.
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2012
Source: Deng, N., Goh, L.-K., Wang, H., Das, K., Tao, J., Tan, I. B., et al. (2012). A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut, 61(5).
Series/Report no.: Gut
Abstract: Objective Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers. Design Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated. Results 22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (FGFR2, ERBB2) and also novel genes in gastric cancer (KLF5, GATA6). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for FGFR2-amplified gastric cancers. Conclusion The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies.
URI: https://hdl.handle.net/10356/100653
http://hdl.handle.net/10220/16299
DOI: http://dx.doi.org/10.1136/gutjnl-2011-301839
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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