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KMID : 0381120160380111085
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Genes and Genomics
2016 Volume.38 No. 11 p.1085 ~ p.1094
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Metastasis associated genomic aberrations in stage II rectal cancer
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Zhao Hong
Shi Zhi-Zhou
Jiang Rui
Zhao Dong-Bing
Zhou Hai-Tao
Liang Jian-Wei
Bi Xin-Yu
Zhao Jian-Jun
Li Zhi-Yu
Zhou Jian-Guo
Huang Zhen
Zhang Ye-Fan
Wang Jian
Xu Xin
Cai Yan
Wang Ming-Rong
Zhang Yu
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Abstract
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Genomic aberrations of rectal carcinoma, especially DNA copy number changes associated with metastasis were largely unclear. We aim to identify the metastasis associated biomarkers in stage II rectal cancer. Formalin-fixed, paraffin-embedded primary tumor tissues of stage II rectal carcinoma were analyzed by array-based comparative genomic hybridization, and genomic aberrations were identified by Genomic Workbench and SAM software. Copy number changes and mRNA expressions were validated by Real-time PCR in an independent rectal cancer samples. The results showed that the most frequent gains in stage II rectal cancer were at 1q21.2-q23.1, 3p21.31, 11q12.2-q23.3, 12q24.11-q24.31, 12q13.11-q14.1 and losses in 18q11.2-q23, 17q21.33-q22, 13q31.1-q31.3, 21q21.1-q21.3, 8p23.3-p23.1 and 4q22.1-q23. Twenty-two amplifications and five homozygous deletions were also identified. We further found that S100A1 (1q21.3-q23.1), MCM7 (7q22.1) and JUND (19p13.11) were amplified and overexpressed in stage II rectal cancer. Interestingly, the genomic aberrations affected 14 signaling pathways including VEGF signaling pathway and fatty acid metabolism. Most importantly, loss of 13q31.1-q34 and gain of 1q44 were associated with distant metastasis. Our results indicated that these metastasis associated genomic changes may be useful to reveal the pathogenesis of rectal cancer metastasis and identify candidate biomarkers.
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KEYWORD
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Array CGH, Rectal cancer, Stage II, Metastasis, Biomarker
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