Genomic variants in mouse model induced by azoxymethane and dextran sodium sulfate improperly mimic human colorectal cancer.
Mouse model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) is generally accepted as an ideal object to study on the carcinogenesis mechanisms of human colorectal cancer (CRC). The genomic responses to the AOM/DSS treatment in mouse that possibly lead to elucidation of CRC pathological mechanism are still poorly understood. For the first time, we investigated the cancer genome landscape of AOM/DSS mouse model by exome sequencing, to testify its molecular faithfulness to human CRC. Of 14 neoplastic samples, 7575 somatic variants were identified, which resulted in 2507 mutant genes and exhibited a large diversity in both colorectal aberrant crypt foci (ACF) and tumors even those tissues that were gained from the similar morphology or same treatment period. Cross-species comparison of the somatic variants demonstrated the totally different patterns of variable sites, mutant genes and perturbed pathways between mouse and human CRC. We therefore come to a conclusion that the tumorigenesis at genomic level in AOM/DSS model may not be properly comparable with that in human CRC, and the molecular mechanism elicited from this animal model should be carefully evaluated.
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, China.
Qingfei
Q
Pan
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Xiaomin
X
Lou
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Ju
J
Zhang
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Yinghui
Y
Zhu
BGI-Shenzhen, Shenzhen, China.
Fuqiang
http://orcid.org/0000-0002-2085-1457
F
Li
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Qiang
Q
Shan
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Xianwei
X
Chen
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Yingying
Y
Xie
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Siyuan
S
Su
Beijing Protein Innovation, Beijing, China.
Hanfu
H
Wei
BGI-Shenzhen, Shenzhen, China.
Liang
L
Lin
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. wul@big.ac.cn.|Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, China. wul@big.ac.cn.
Lin
L
Wu
CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. siqiliu@big.ac.cn.|Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, China. siqiliu@big.ac.cn.|BGI-Shenzhen, Shenzhen, China. siqiliu@big.ac.cn.
Siqi
S
Liu
D058739:Aberrant Crypt Foci / Q000235:genetics; D000818:Animals; D001397:Azoxymethane; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D016264:Dextran Sulfate; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL / Q000235:genetics; D009154:Mutation; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics*; D000073359:Exome Sequencing
D016264:Dextran Sulfate; D001397:Azoxymethane