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Complex clonal mosaicism within microdissected intestinal metaplastic glands without concurrent gastric cancer
  1. Yan Guo1,2,
  2. Ayuan Huang3,
  3. Chuansheng Hu1,
  4. Yan Zhou3,
  5. Xiaodan Zhang1,
  6. Daniel M Czajkowsky1,
  7. Jianfang Li4,
  8. Shidan Cheng5,
  9. Ruizhe Shen5,
  10. Jianren Gu2,
  11. Bingya Liu4,
  12. Zhifeng Shao1,2
  1. 1Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China
  2. 2State Key Laboratory for Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, P. R. China
  3. 3Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, P. R. China
  4. 4Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China
  5. 5Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China
  1. Correspondence to Professor Zhifeng Shao, School of Biomedical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China; zfshao{at}sjtu.edu.cn Professor Bingya Liu, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Ruijin No 2 Road, Shanghai 200240, P. R. China; liubingya{at}sjtu.edu.cn

Abstract

Background The transformation of healthy gastric tissue into intestinal metaplasia (IM) is thought to be a critical premalignant step in the development of intestinal-type gastric adenocarcinoma (GA). How such premalignancies contribute to the development of GA is, however, poorly understood.

Methods In this study, the extent and clonal complexity in IM tissue from patients without gastric cancer were analysed by measuring variations of multiple microsatellite (MS) markers.

Results Even though these tissues are generally regarded as clinically benign, we found extensive MS length heterogeneity between and within individual IM glands, indicating that complex genome diversity is already pervasive in these tissues. Based on a clonal relationship analysis, we found that there exist multiple clones within individual IM glands and that MS alterations can accumulate in these clones. Moreover, we found spatially distant IM glands with the same MS phenotype, suggesting that these MS alterations were progressed by gland fission.

Conclusions These results provide evidence that genetic instability is an early event, present within metaplastic tissues of otherwise non-cancer patients, and such frequent genetic alterations can be part of the pathophysiological rationale for the requirement of this phase during gastric carcinogenesis.

  • Stomach
  • Intestinal metaplasia
  • Laser capture microdissection
  • Microsatellite markers
  • genetic mosaicism

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