Novel recurrent genetic imbalances in human hepatocellular carcinoma cell lines identified by comparative genomic hybridization

被引:103
作者
Zimonjic, DB [1 ]
Keck, CL [1 ]
Thorgeirsson, SS [1 ]
Popescu, NC [1 ]
机构
[1] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1002/hep.510290410
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
To search for recurrent and specific genomic alterations in human hepatocellular carcinoma (HCC), we examined 18 cell lines by comparative genomic hybridization (CGH), a molecular cytogenetic approach that allows positional identification of gains and losses of DNA sequences of the entire tumor genome. We report here a distinct pattern of multiple recurrent DNA copy-number gains and losses that include alterations frequently seen in other neoplasias as well as changes potentially specific for HCC. The most frequent gains were localized on 1p34.3-35, 1p33-34.1, 1q21-23, 1q31-32, 6p11-12, 7p21, 7q11.2, 8q24.1-24.2, 11q11-13, 12q11-13, 12q23, 17q11.2-21, 17q23-24, and 20p11.1-q13.2. Recurrent losses were mapped on 3p12-14, 3q25, 4p12-14, 4q13-34, 5q21, 6q25-26, 8p11.2-23, 9p12-24, 11q23-24, 13q12-33, 14q12-13, 15q25-26, 18q11.2-22.2, and 21q21-22. Seventeen genomic imbalances are novel in HCC, thus extending significantly the map of genetic changes and providing a starting point for the isolation of new genes relevant in pathogenesis of liver neoplasia, as well as providing molecular probes for both diagnosis and monitoring treatment of the disease.
引用
收藏
页码:1208 / 1214
页数:7
相关论文
共 73 条
[1]  
Bentz M, 1998, GENE CHROMOSOME CANC, V21, P172, DOI 10.1002/(SICI)1098-2264(199802)21:2<172::AID-GCC14>3.3.CO
[2]  
2-T
[3]   Frequency of mutation and deletion of the tumor suppressor gene CDKN2A (MTS1/p16) in hepatocellular carcinoma from an Australian population [J].
Biden, K ;
Young, J ;
Buttenshaw, R ;
Searle, J ;
Cooksley, G ;
Xu, DB ;
Leggett, B .
HEPATOLOGY, 1997, 25 (03) :593-597
[4]   THE MOLECULAR-GENETICS OF CANCER [J].
BISHOP, JM .
SCIENCE, 1987, 235 (4786) :305-311
[5]   APOPTOTIC CELL-DEATH INDUCED BY C-MYC IS INHIBITED BY BCL-2 [J].
BISSONNETTE, RP ;
ECHEVERRI, F ;
MAHBOUBI, A ;
GREEN, DR .
NATURE, 1992, 359 (6395) :552-554
[6]  
Boige V, 1997, CANCER RES, V57, P1986
[7]  
BOSCH FX, 1991, ADV AP BIOT, V13, P35
[8]   LOSS OF HETEROZYGOSITY SUGGESTS TUMOR SUPPRESSOR GENE RESPONSIBLE FOR PRIMARY HEPATOCELLULAR-CARCINOMA [J].
BUETOW, KH ;
MURRAY, JC ;
ISRAEL, JL ;
LONDON, WT ;
SMITH, M ;
KEW, M ;
BLANQUET, V ;
BRECHOT, C ;
REDEKER, A ;
GOVINDARAJAH, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (22) :8852-8856
[9]   Isolation of 45 exon-like fragments from 8p22->p21.3, a region that is commonly deleted in hepatocellular, colorectal, and non-small cell lung carcinomas [J].
Chinen, K ;
Isomura, M ;
Izawa, K ;
Fujiwara, Y ;
Ohata, H ;
Iwamasa, T ;
Nakamura, Y .
CYTOGENETICS AND CELL GENETICS, 1996, 75 (2-3) :190-196
[10]   M6P/IGF2R GENE IS MUTATED IN HUMAN HEPATOCELLULAR CARCINOMAS WITH LOSS OF HETEROZYGOSITY [J].
DESOUZA, AT ;
HANKINS, GR ;
WASHINGTON, MK ;
ORTON, TC ;
JIRTLE, RL .
NATURE GENETICS, 1995, 11 (04) :447-449