Array-Based Comparative Genomic Hybridization Identifies Localized DNA Amplifications and Homozygous Deletions in Pancreatic Cancer
Pancreatic cancer, the fourth leading cause of cancer death in the United States, is frequently associated with the amplification and deletion of specific oncogenes and tumor-suppressor genes (TSGs), respectively. To identify such novel alterations and to discover the underlying genes, we performed...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2005-06-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558605800764 |
| id |
doaj-a08843602edd4c5996e68b59a7bdd279 |
|---|---|
| record_format |
Article |
| spelling |
doaj-a08843602edd4c5996e68b59a7bdd2792020-11-25T00:06:30ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022005-06-017655656210.1593/neo.04586Array-Based Comparative Genomic Hybridization Identifies Localized DNA Amplifications and Homozygous Deletions in Pancreatic CancerMurali D. Bashyam0Ryan Bair1Young H. Kim2Pei Wang3Tina Hernandez-Boussard4Collins A. Karikari5Robert Tibshirani6Anirban Maitra7Jonathan R. Pollack8Department of Pathology, Stanford University, Stanford, CA, USADepartment of Pathology, Stanford University, Stanford, CA, USADepartment of Pathology, Stanford University, Stanford, CA, USADepartment of Statistics, Stanford University, Stanford, CA, USADepartment of Genetics, Stanford University, Stanford, CA, USADepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USADepartment of Statistics, Stanford University, Stanford, CA, USADepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USADepartment of Pathology, Stanford University, Stanford, CA, USA Pancreatic cancer, the fourth leading cause of cancer death in the United States, is frequently associated with the amplification and deletion of specific oncogenes and tumor-suppressor genes (TSGs), respectively. To identify such novel alterations and to discover the underlying genes, we performed comparative genomic hybridization on a set of 22 human pancreatic cancer cell lines, using cDNA microarrays measuring ~ 26,000 human genes (thereby providing an average mapping resolution of <60 kb). To define the subset of amplified and deleted genes with correspondingly altered expression, we also profiled mRNA levels in parallel using the same cDNA microarray platform. In total, we identified 14 high-level amplifications (38–4934 kb in size) and 15 homozygous deletions (46–725 kb). We discovered novel localized amplicons, suggesting previously unrecognized candidate oncogenes at 6p21, 7q21 (SMURF1, TRRAP), 11q22 (BIRC2, BIRC3), 12p12, 14q24 (TGFB3), 17ql2, and 19q13. Likewise, we identified novel polymerase chain reaction-validated homozygous deletions indicating new candidate TSGs at 6q25, 8p23, 8p22 (TUSC3), 9q33 (TNC, TNFSF15),10q22, 10q24 (CHUK), 11p15 (DKK3), 16q23, 18q23, 21q22 (PRDM15, ANKRD3), and Xp1l. Our findings suggest candidate genes and pathways, which may contribute to the development or progression of pancreatic cancer. http://www.sciencedirect.com/science/article/pii/S1476558605800764Pancreatic cancerarray CGHcomparative genomic hybridizationexpression profilingDNA amplification |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Murali D. Bashyam Ryan Bair Young H. Kim Pei Wang Tina Hernandez-Boussard Collins A. Karikari Robert Tibshirani Anirban Maitra Jonathan R. Pollack |
| spellingShingle |
Murali D. Bashyam Ryan Bair Young H. Kim Pei Wang Tina Hernandez-Boussard Collins A. Karikari Robert Tibshirani Anirban Maitra Jonathan R. Pollack Array-Based Comparative Genomic Hybridization Identifies Localized DNA Amplifications and Homozygous Deletions in Pancreatic Cancer Neoplasia: An International Journal for Oncology Research Pancreatic cancer array CGH comparative genomic hybridization expression profiling DNA amplification |
| author_facet |
Murali D. Bashyam Ryan Bair Young H. Kim Pei Wang Tina Hernandez-Boussard Collins A. Karikari Robert Tibshirani Anirban Maitra Jonathan R. Pollack |
| author_sort |
Murali D. Bashyam |
| title |
Array-Based Comparative Genomic Hybridization Identifies Localized DNA Amplifications and Homozygous Deletions in Pancreatic Cancer |
| title_short |
Array-Based Comparative Genomic Hybridization Identifies Localized DNA Amplifications and Homozygous Deletions in Pancreatic Cancer |
| title_full |
Array-Based Comparative Genomic Hybridization Identifies Localized DNA Amplifications and Homozygous Deletions in Pancreatic Cancer |
| title_fullStr |
Array-Based Comparative Genomic Hybridization Identifies Localized DNA Amplifications and Homozygous Deletions in Pancreatic Cancer |
| title_full_unstemmed |
Array-Based Comparative Genomic Hybridization Identifies Localized DNA Amplifications and Homozygous Deletions in Pancreatic Cancer |
| title_sort |
array-based comparative genomic hybridization identifies localized dna amplifications and homozygous deletions in pancreatic cancer |
| publisher |
Elsevier |
| series |
Neoplasia: An International Journal for Oncology Research |
| issn |
1476-5586 1522-8002 |
| publishDate |
2005-06-01 |
| description |
Pancreatic cancer, the fourth leading cause of cancer death in the United States, is frequently associated with the amplification and deletion of specific oncogenes and tumor-suppressor genes (TSGs), respectively. To identify such novel alterations and to discover the underlying genes, we performed comparative genomic hybridization on a set of 22 human pancreatic cancer cell lines, using cDNA microarrays measuring ~ 26,000 human genes (thereby providing an average mapping resolution of <60 kb). To define the subset of amplified and deleted genes with correspondingly altered expression, we also profiled mRNA levels in parallel using the same cDNA microarray platform. In total, we identified 14 high-level amplifications (38–4934 kb in size) and 15 homozygous deletions (46–725 kb). We discovered novel localized amplicons, suggesting previously unrecognized candidate oncogenes at 6p21, 7q21 (SMURF1, TRRAP), 11q22 (BIRC2, BIRC3), 12p12, 14q24 (TGFB3), 17ql2, and 19q13. Likewise, we identified novel polymerase chain reaction-validated homozygous deletions indicating new candidate TSGs at 6q25, 8p23, 8p22 (TUSC3), 9q33 (TNC, TNFSF15),10q22, 10q24 (CHUK), 11p15 (DKK3), 16q23, 18q23, 21q22 (PRDM15, ANKRD3), and Xp1l. Our findings suggest candidate genes and pathways, which may contribute to the development or progression of pancreatic cancer.
|
| topic |
Pancreatic cancer array CGH comparative genomic hybridization expression profiling DNA amplification |
| url |
http://www.sciencedirect.com/science/article/pii/S1476558605800764 |
| work_keys_str_mv |
AT muralidbashyam arraybasedcomparativegenomichybridizationidentifieslocalizeddnaamplificationsandhomozygousdeletionsinpancreaticcancer AT ryanbair arraybasedcomparativegenomichybridizationidentifieslocalizeddnaamplificationsandhomozygousdeletionsinpancreaticcancer AT younghkim arraybasedcomparativegenomichybridizationidentifieslocalizeddnaamplificationsandhomozygousdeletionsinpancreaticcancer AT peiwang arraybasedcomparativegenomichybridizationidentifieslocalizeddnaamplificationsandhomozygousdeletionsinpancreaticcancer AT tinahernandezboussard arraybasedcomparativegenomichybridizationidentifieslocalizeddnaamplificationsandhomozygousdeletionsinpancreaticcancer AT collinsakarikari arraybasedcomparativegenomichybridizationidentifieslocalizeddnaamplificationsandhomozygousdeletionsinpancreaticcancer AT roberttibshirani arraybasedcomparativegenomichybridizationidentifieslocalizeddnaamplificationsandhomozygousdeletionsinpancreaticcancer AT anirbanmaitra arraybasedcomparativegenomichybridizationidentifieslocalizeddnaamplificationsandhomozygousdeletionsinpancreaticcancer AT jonathanrpollack arraybasedcomparativegenomichybridizationidentifieslocalizeddnaamplificationsandhomozygousdeletionsinpancreaticcancer |
| _version_ |
1725421713114529792 |