TY - JOUR T1 - A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets JF - Gut JO - Gut SP - 673 LP - 684 DO - 10.1136/gutjnl-2011-301839 VL - 61 IS - 5 AU - Niantao Deng AU - Liang Kee Goh AU - Hannah Wang AU - Kakoli Das AU - Jiong Tao AU - Iain Beehuat Tan AU - Shenli Zhang AU - Minghui Lee AU - Jeanie Wu AU - Kiat Hon Lim AU - Zhengdeng Lei AU - Glenn Goh AU - Qing-Yan Lim AU - Angie Lay-Keng Tan AU - Dianne Yu Sin Poh AU - Sudep Riahi AU - Sandra Bell AU - Michael M Shi AU - Ronald Linnartz AU - Feng Zhu AU - Khay Guan Yeoh AU - Han Chong Toh AU - Wei Peng Yong AU - Hyun Cheol Cheong AU - Sun Young Rha AU - Alex Boussioutas AU - Heike Grabsch AU - Steve Rozen AU - Patrick Tan Y1 - 2012/05/01 UR - http://gut.bmj.com/content/61/5/673.abstract N2 - 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. ER -