Integrated analysis of copy number alterations and loss of heterozygosity in human pancreatic cancer using a high-resolution, single nucleotide polymorphism array.
OBJECTIVE
To chart molecular genetic events in pancreatic cancer.


METHODS
We analyzed genome-wide copy number alterations and loss of heterozygosity (LOH) in 25 established pancreatic cancer cell lines using a high-density single nucleotide polymorphism (SNP) array. We verified the data using genomic PCR and applied them to clinical samples.


RESULTS
Twenty-six homozygous deletion regions were detected in at least 1 cell line and LOH was found at 9p, 18q, 17p, 8p, 13q, 6q, 3p, 6p, 22q, 9q and 12q with high frequency (>50%), consistent with a previous study. Moreover, we found 23 amplified regions in at least 2 cell lines, including 8 unreported loci. We then examined representative genes at the 8 amplified loci in matched pairs of pancreatic cancer and normal tissues. The amplification was detected in 1 (7.1%) to 5 (35.7%) of 14 microdissected tissue specimens.


CONCLUSIONS
Using high-resolution SNP arrays, we studied genome-wide copy number alterations and LOH simultaneously. We identified several novel and minute genomic amplifications, which contained candidate oncogenes in human pancreatic cancers.
Lin
Lian-Jie
LJ
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Asaoka
Yoshinari
Y
Tada
Motohisa
M
Sanada
Masashi
M
Nannya
Yasuhito
Y
Tanaka
Yasuo
Y
Tateishi
Keisuke
K
Ohta
Miki
M
Seto
Motoko
M
Sasahira
Naoki
N
Tada
Minoru
M
Kawabe
Takao
T
Zheng
Chang-Qing
CQ
Kanai
Fumihiko
F
Ogawa
Seishi
S
Omata
Masao
M
D045744:Cell Line, Tumor; D018628:Gene Dosage; D006801:Humans; D019656:Loss of Heterozygosity; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide