Detection Of DNA Copy Number Alterations In Pancreatic Ductal Adenocarcinoma

【Background and Purpose】DNA copy number alterations play an important role in the initiation and progression of pancreatic ductal adenocarcinoma(PDAC).There have been some reports on DNA changes of PDAC detected by BAC-based array comparative genomic hybridization(array CGH),but most of them were performed on pancreatic cancer cell lines.In the present study,we used oligonucleotide array CGH to identify genetic alterations of PDAC genome.【Patients and Methods】The tissue samples were obtained from 15 PDAC.Tumor cells collected by microdissection and genomic DNA were isolated.Array CGH was performed with the Agilent Human Genome CGH 44B array.DNA copy number alterations of PDAC were validated by fluorescence in situ hybridization(FISH) and real-time PCR.Tissue microarray was constructed,containing 65 PDAC and 8 chronic pancreatitis tissues.The expression of PSCA and HMGA2 proteins were detected by using immunohistochemical method and the relationships between the proteins expression and clinicopathological parameters of PDAC were analyzed.【Results】Profiles of 15 PDAC identified multiple chromosomal regions with DNA copy number alterations.Loci with(＞80%cases) gains were at 1q31.3,3p22.1,3p22.31, 3p22.3,8q24.3,10q11.23,14q12,16p13.3,17q24.1,Xp11.21,and Xq28.Eighty genes were amplified in≥4 out of 15 cases(＞20%).The most frequent losses(＞80%) were at 5p13.3,12q13.13,17p13.1,17q21.31,and Xq11.1.One hundred and forty-four loci with deletions were detected(＞20.0%).Q-PCR and FISH results confirmed that the PSCA gene was of amplification.IHC analysis showed that PSCA and HMGA2 expressed in 67.2%and 76.7%of tumors,respectively.The positive expression of PSCA and HMGA2 was associated with lymph node metastases(PSCA:x~2=4.370,P=0.037;HMGA2:x~2= 13.062,P=0.001).【Conclusions】There existed lots of chromosomal loci with frequent alterations of DNA copy number in PDAC.PSCA and HMGA2 might be two useful biomarkers in more advanced stage of PDAC.