Genome-wide aberrations in pancreatic adenocarcinoma
- 作者：Norma J. Nowak ; Daniel Gaile ; Jeffrey M. Conroy ; Devin McQuaid ; John Cowell ; Randy Carter ; Michael G. Goggins ; Ralph H. Hruban and Anirban Maitra
- 刊名：Cancer Genetics and Cytogenetics
- 出版年：2005
- 期刊代码：43_01654608
- 类别：med
- 出版时间：2005
- 卷：161
- 期：1
- 页码：36-50
- 文件大小：737 K
摘要
Chromosomal instability, manifesting as copy number alterations (CNAs), is characteristic of pancreatic adenocarcinoma. We used bacterial artificial chromosome (BAC) array-based comparative genomic hybridization (aCGH) to examine the pancreatic adenocarcinoma genome for submicroscopic amplifications and deletions. Profiles of 33 samples (17 first-passage xenografts and 16 cell lines) identified numerous chromosomal regions with CNAs, including losses at 1p36.33
p34.3, 1p13.3p13.2, 3p26, 3p25.2p22.3, 3p22.1p14.1, 4q28.3, 4q31, 4q35.1, 5q14.3, 6p, 6q, 8p23.3p12, 9p, 9q22.32q31.1, 13q33.2, 15q11.2, 16p13.3, 17p, 18q11.21q23 , 19p13.3p13.12, 19q13.2, 21p, 21q, and 22p, 22q and gains at 7p21.1p11.2, 7q31.32, 7q33, 8q11.1q24, 11p13, 14q22.2, 20p12.2, and 20q11.23q13.33. Novel regions containing CNAs were identified and refined by combining the increased resolution of our BAC CGH array with a statistical algorithm developed for assigning significance values to altered BACs across samples. A subset of array-based CNAs was validated using polymerase chain reaction 13;based techniques, immunohistochemistry and fluorescence in situ hybridization. BAC aCGH proved to be a powerful genome-wide strategy to identify molecular alterations in pancreatic cancer and to distinguish differences between cell line and xenograft aberration profiles. These findings should greatly facilitate further research in understanding the pathogenesis of this lethal disease, and could lead to the identification of novel therapeutic targets and biomarkers for early detection.
p34.3, 1p13.3p13.2, 3p26, 3p25.2p22.3, 3p22.1p14.1, 4q28.3, 4q31, 4q35.1, 5q14.3, 6p, 6q, 8p23.3p12, 9p, 9q22.32q31.1, 13q33.2, 15q11.2, 16p13.3, 17p, 18q11.21q23 , 19p13.3p13.12, 19q13.2, 21p, 21q, and 22p, 22q and gains at 7p21.1p11.2, 7q31.32, 7q33, 8q11.1q24, 11p13, 14q22.2, 20p12.2, and 20q11.23q13.33. Novel regions containing CNAs were identified and refined by combining the increased resolution of our BAC CGH array with a statistical algorithm developed for assigning significance values to altered BACs across samples. A subset of array-based CNAs was validated using polymerase chain reaction 13;based techniques, immunohistochemistry and fluorescence in situ hybridization. BAC aCGH proved to be a powerful genome-wide strategy to identify molecular alterations in pancreatic cancer and to distinguish differences between cell line and xenograft aberration profiles. These findings should greatly facilitate further research in understanding the pathogenesis of this lethal disease, and could lead to the identification of novel therapeutic targets and biomarkers for early detection.