Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: identification of genetic indicators that predict patient outcome.
We analyzed the subchromosomal numerical aberrations of 44 surgically resected pancreatic adenocarcinomas by array-based comparative genomic hybridization. The aberration profile ranged widely between cases, suggesting the presence of multiple or complementary mechanisms of evolution in pancreatic cancer, and was associated with lymph node metastasis and venous or serosal invasion. A large number of small loci, previously uncharacterized in pancreatic cancer, showed non-random loss or gain. Frequent losses at 1p36, 4p16, 7q36, 9q34, 11p15, 11q13, 14q32-33, 16p13, 17p11-13, 17q11-25, 18q21-tel, 19p13, 21q22 and 22q11-12, and gains at 1q25, 2p16, 2q21-37, 3q25, 5p14, 5q11-13, 7q21, 7p22, 8p22, 8q21-23, 10q21, 12p13, 13q22, 15q13-22 and 18q11 were identified. Sixteen loci were amplified recurrently. We identified novel chromosomal alterations that were significantly associated with a range of malignant phenotypes. Gain of LUNX, HCK, E2F1 and DNMT3b at 20q11, loss of p73 at 1p36 and gain of PPM1D at 17q23 independently predicted patient outcome. Expression profiling of amplified genes identified Smurf1 and TRRAP at 7q22.1, BCAS1 at 20q13.2-3, and VCL at 10q22.1 as potential novel oncogenes. Our results contribute to a complete description of genomic structural aberrations and the identification of potential therapeutic targets and genetic indicators that predict patient outcome in pancreatic adenocarcinoma.
Loukopoulos
Panayiotis
P
Pathology Division, National Cancer Center Research Institute, 51-1, Tsukiji, Chuo-ku, Tokyo, USA.
Shibata
Tatsuhiro
T
Katoh
Hiroto
H
Kokubu
Akiko
A
Sakamoto
Michiie
M
Yamazaki
Ken
K
Kosuge
Tomoo
T
Kanai
Yae
Y
Hosoda
Fumie
F
Imoto
Issei
I
Ohki
Misao
M
Inazawa
Jyoji
J
Hirohashi
Setsuo
S
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D006824:Hybridization, Genetic; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate