BACKGROUND AND AIMS: The recent advancement of next-generation sequencing (NGS) has enabled the identification of cancer-related somatic aberrations in advanced gastric cancer. However, these remain unclear in early gastric cancers, especially in intramucosal gastric cancers. PATIENTS AND METHODS: Thirty-one well-differentiated (tub1) intramucosal gastric cancers obtained by endoscopic submucosal dissection (ESD) from 29 patients were analyzed. After precise collection of tumors and non-tumors from formalin-fixed paraffin-embedded tissues using laser-captured microdissection (LCM), target sequencing analysis of 50 cancer-related genes was performed using an Ion-Proton sequencer. RESULTS: The most frequent hotspot mutation was found in TP53 (17 lesions, 54.8%) followed by the Wnt-signaling pathway genes, APC and CTNNB1 (6 lesions, 19.4%). The mutations in TP53 and the Wnt-signaling genes were mutually exclusive (p = 0.004). There was a tendency that H. pylori infection (p = 0.082) and macroscopic protrusion (p = 0.095) was associated with the presence of these mutations. Only 10 lesions (59%) among 17 lesions with proven TP53 mutations were positive for p53 immunostaining demonstrating the superiority of the mutational analysis. In addition, focal gene amplification of ERBB2 (16%) was found frequently in these early stage lesions. CONCLUSIONS: Using LCM and NGS, mutations in TP53 and the Wnt-signaling pathway were frequently found and were mutually exclusive in the earliest stage of gastric carcinogenesis.
BACKGROUND AND AIMS: The recent advancement of next-generation sequencing (NGS) has enabled the identification of cancer-related somatic aberrations in advanced gastric cancer. However, these remain unclear in early gastric cancers, especially in intramucosal gastric cancers. PATIENTS AND METHODS: Thirty-one well-differentiated (tub1) intramucosal gastric cancers obtained by endoscopic submucosal dissection (ESD) from 29 patients were analyzed. After precise collection of tumors and non-tumors from formalin-fixed paraffin-embedded tissues using laser-captured microdissection (LCM), target sequencing analysis of 50 cancer-related genes was performed using an Ion-Proton sequencer. RESULTS: The most frequent hotspot mutation was found in TP53 (17 lesions, 54.8%) followed by the Wnt-signaling pathway genes, APC and CTNNB1 (6 lesions, 19.4%). The mutations in TP53 and the Wnt-signaling genes were mutually exclusive (p = 0.004). There was a tendency that H. pyloriinfection (p = 0.082) and macroscopic protrusion (p = 0.095) was associated with the presence of these mutations. Only 10 lesions (59%) among 17 lesions with proven TP53 mutations were positive for p53 immunostaining demonstrating the superiority of the mutational analysis. In addition, focal gene amplification of ERBB2 (16%) was found frequently in these early stage lesions. CONCLUSIONS: Using LCM and NGS, mutations in TP53 and the Wnt-signaling pathway were frequently found and were mutually exclusive in the earliest stage of gastric carcinogenesis.
Authors: Kai Wang; Junsuo Kan; Siu Tsan Yuen; Stephanie T Shi; Kent Man Chu; Simon Law; Tsun Leung Chan; Zhengyan Kan; Annie S Y Chan; Wai Yin Tsui; Siu Po Lee; Siu Lun Ho; Anthony K W Chan; Grace H W Cheng; Peter C Roberts; Paul A Rejto; Neil W Gibson; David J Pocalyko; Mao Mao; Jiangchun Xu; Suet Yi Leung Journal: Nat Genet Date: 2011-10-30 Impact factor: 38.330
Authors: Kai Wang; Siu Tsan Yuen; Jiangchun Xu; Siu Po Lee; Helen H N Yan; Stephanie T Shi; Hoi Cheong Siu; Shibing Deng; Kent Man Chu; Simon Law; Kok Hoe Chan; Annie S Y Chan; Wai Yin Tsui; Siu Lun Ho; Anthony K W Chan; Jonathan L K Man; Valentina Foglizzo; Man Kin Ng; April S Chan; Yick Pang Ching; Grace H W Cheng; Tao Xie; Julio Fernandez; Vivian S W Li; Hans Clevers; Paul A Rejto; Mao Mao; Suet Yi Leung Journal: Nat Genet Date: 2014-05-11 Impact factor: 38.330