Complex clonal mosaicism within microdissected intestinal metaplastic glands without concurrent gastric cancer.
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.



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.



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.



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.
Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China State Key Laboratory for Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, P. R. China.
Yan
Y
Guo
Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Ayuan
A
Huang
Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China.
Chuansheng
C
Hu
Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Yan
Y
Zhou
Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China.
Xiaodan
X
Zhang
Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China.
Daniel M
DM
Czajkowsky
Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Jianfang
J
Li
Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Shidan
S
Cheng
Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Ruizhe
R
Shen
State Key Laboratory for Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, P. R. China.
Jianren
J
Gu
Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Bingya
B
Liu
Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China State Key Laboratory for Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, P. R. China.
Zhifeng
Z
Shao
D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*
Intestinal metaplasia; Laser capture microdissection; Microsatellite markers; Stomach; genetic mosaicism