title: Identification of genomic alterations in pancreatic cancer using array-based comparative genomic hybridization.
abstract: BACKGROUND
  Genomic aberration is a common feature of human cancers and also is one of the basic mechanisms that lead to overexpression of oncogenes and underexpression of tumor suppressor genes. Our study aims to identify frequent genomic changes in pancreatic cancer.
  
  
  METHODS
  We used array comparative genomic hybridization (array CGH) to identify recurrent genomic alterations and validated the protein expression of selected genes by immunohistochemistry.
  
  
  RESULTS
  Sixteen gains and thirty-two losses occurred in more than 30% and 60% of the tumors, respectively. High-level amplifications at 7q21.3-q22.1 and 19q13.2 and homozygous deletions at 1p33-p32.3, 1p22.1, 1q22, 3q27.2, 6p22.3, 6p21.31, 12q13.2, 17p13.2, 17q21.31 and 22q13.1 were identified. Especially, amplification of AKT2 was detected in two carcinomas and homozygous deletion of CDKN2C in other two cases. In 15 independent validation samples, we found that AKT2 (19q13.2) and MCM7 (7q22.1) were amplified in 6 and 9 cases, and CAMTA2 (17p13.2) and PFN1 (17p13.2) were homozygously deleted in 3 and 1 cases. AKT2 and MCM7 were overexpressed, and CAMTA2 and PFN1 were underexpressed in pancreatic cancer tissues than in morphologically normal operative margin tissues. Both GISTIC and Genomic Workbench software identified 22q13.1 containing APOBEC3A and APOBEC3B as the only homozygous deletion region. And the expression levels of APOBEC3A and APOBEC3B were significantly lower in tumor tissues than in morphologically normal operative margin tissues. Further validation showed that overexpression of PSCA was significantly associated with lymph node metastasis, and overexpression of HMGA2 was significantly associated with invasive depth of pancreatic cancer.
  
  
  CONCLUSIONS
  These recurrent genomic changes may be useful for revealing the mechanism of pancreatic carcinogenesis and providing candidate biomarkers.
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Liang
authors.affiliation: Faculty of Medicine, Kunming University of Science and Technology, Kunming, China.
authors.forename: Zhi-Zhou
authors.initials: ZZ
authors.lastname: Shi
authors.affiliation: Faculty of Medicine, Kunming University of Science and Technology, Kunming, China.
authors.forename: Tian-Yun
authors.initials: TY
authors.lastname: Shen
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Che
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Su-Sheng
authors.initials: SS
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Wang
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D025743:HMGA2 Protein; D009363:Neoplasm Proteins; C110843:PSCA protein, human