Abstract
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, 1p13.3∼p13.2, 3p26, 3p25.2∼p22.3, 3p22.1∼p14.1, 4q28.3, 4q31, 4q35.1, 5q14.3, 6p, 6q, 8p23.3∼p12, 9p, 9q22.32∼q31.1, 13q33.2, 15q11.2, 16p13.3, 17p, 18q11.21∼q23 , 19p13.3∼p13.12, 19q13.2, 21p, 21q, and 22p, 22q and gains at 7p21.1∼p11.2, 7q31.32, 7q33, 8q11.1∼q24, 11p13, 14q22.2, 20p12.2, and 20q11.23∼q13.33. 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-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 36-50 |
| Number of pages | 15 |
| Journal | Cancer Genetics and Cytogenetics |
| Volume | 161 |
| Issue number | 1 |
| DOIs | |
| State | Published - Aug 1 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
Cite this
Genome-wide aberrations in pancreatic adenocarcinoma. / Nowak, Norma J.; Gaile, Daniel; Conroy, Jeffrey M.; McQuaid, Devin; Cowell, John Kenneth; Carter, Randy; Goggins, Michael G.; Hruban, Ralph H.; Maitra, Anirban.
In: Cancer Genetics and Cytogenetics, Vol. 161, No. 1, 01.08.2005, p. 36-50.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genome-wide aberrations in pancreatic adenocarcinoma
AU - Nowak, Norma J.
AU - Gaile, Daniel
AU - Conroy, Jeffrey M.
AU - McQuaid, Devin
AU - Cowell, John Kenneth
AU - Carter, Randy
AU - Goggins, Michael G.
AU - Hruban, Ralph H.
AU - Maitra, Anirban
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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, 1p13.3∼p13.2, 3p26, 3p25.2∼p22.3, 3p22.1∼p14.1, 4q28.3, 4q31, 4q35.1, 5q14.3, 6p, 6q, 8p23.3∼p12, 9p, 9q22.32∼q31.1, 13q33.2, 15q11.2, 16p13.3, 17p, 18q11.21∼q23 , 19p13.3∼p13.12, 19q13.2, 21p, 21q, and 22p, 22q and gains at 7p21.1∼p11.2, 7q31.32, 7q33, 8q11.1∼q24, 11p13, 14q22.2, 20p12.2, and 20q11.23∼q13.33. 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-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.
AB - 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, 1p13.3∼p13.2, 3p26, 3p25.2∼p22.3, 3p22.1∼p14.1, 4q28.3, 4q31, 4q35.1, 5q14.3, 6p, 6q, 8p23.3∼p12, 9p, 9q22.32∼q31.1, 13q33.2, 15q11.2, 16p13.3, 17p, 18q11.21∼q23 , 19p13.3∼p13.12, 19q13.2, 21p, 21q, and 22p, 22q and gains at 7p21.1∼p11.2, 7q31.32, 7q33, 8q11.1∼q24, 11p13, 14q22.2, 20p12.2, and 20q11.23∼q13.33. 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-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.
UR - http://www.scopus.com/inward/record.url?scp=23244467697&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23244467697&partnerID=8YFLogxK
U2 - 10.1016/j.cancergencyto.2005.01.009
DO - 10.1016/j.cancergencyto.2005.01.009
M3 - Article
C2 - 16080956
AN - SCOPUS:23244467697
VL - 161
SP - 36
EP - 50
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
SN - 0165-4608
IS - 1
ER -