Metastasis associated genomic aberrations in stage II rectal cancer
Zhao, H., Peking Union Medical College, Beijing, China | Shi, Z.Z., Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China | Jiang, R., First People's Hospital of Yunnan Province, Kunming, China | Zhao, D.B., Peking Union Medical College, Beijing, China | Zhou, H.T., Peking Union Medical College, Beijing, China | Liang, J.W., Peking Union Medical College, Beijing, China | Bi, X.Y., Peking Union Medical College, Beijing, China | Zhao, J.J., Peking Union Medical College, Beijing, China | Li, Z.Y., Peking Union Medical College, Beijing, China | Zhou, J.G., Peking Union Medical College, Beijing, China | Huang, Z., Peking Union Medical College, Beijing, China | Zhang, Y.F., Peking Union Medical College, Beijing, China | Wang, J., Peking Union Medical College, Beijing, China | Xu, X., Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China | Cai, Y., Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China | Wang, M.R., Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China | Zhang, Y., Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
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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