Comparative mutational analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas

被引:112
作者
MacGrogan, D
Pegram, M
Slamon, D
Bookstein, R
机构
[1] CANJI INC,DEPT BIOL MOL,SAN DIEGO,CA 92121
[2] UNIV CALIF LOS ANGELES,SCH MED,DIV HEMATOL ONCOL,LOS ANGELES,CA 90095
关键词
tumor suppressor gene; DPC4; mutation; prostate cancer; colorectal cancer;
D O I
10.1038/sj.onc.1201232
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Allelic deletions of chromosome 18q are reported to be common in prostate and colorectal cancers, suggesting that one or more tumor suppressor genes on 18q are involved in the genesis of these neoplasms, The DPC4 gene, a recently identified candidate tumor suppressor in 18q21, was examined for evidence of inactivation in prostatic carcinomas, and results compared to those of a parallel analysis of colorectal carcinomas, for which DPC4 mutation has been reported in similar to 10% of cases, In this study, only three (10%) of 29 informative primary prostate cancers showed allelic loss of chromosome 18q21 markers, and no point mutations or deletions of DPC4 were detected in the complete set of 45 primary or metastatic cases, In contrast, five (56%) of nine primary colorectal tumors displayed allelic loss of 18q markers and in one of these a somatically acquired G-->T missense mutation was found in exon 1. Of twelve colorectal tumor cell lines, one showed a G-->C missense mutation in exon 8 and two had partial homozygous deletions that would likely abrogate gene function, These data suggest that DPC4 is rarely if ever mutated during prostatic oncogenesis, whereas inactivation of this gene may contribute to the genesis of a subset of colorectal carcinomas.
引用
收藏
页码:1111 / 1114
页数:4
相关论文
共 30 条
[1]  
BOOKSTEIN R, 1993, CANCER RES, V53, P3369
[2]   SOMATIC ALLELIC LOSS AT THE DCC, APC, NM23-H1 AND P53 TUMOR-SUPPRESSOR GENE LOCI IN HUMAN PROSTATIC-CARCINOMA [J].
BREWSTER, SF ;
BROWNE, S ;
BROWN, KW .
JOURNAL OF UROLOGY, 1994, 151 (04) :1073-1077
[3]   ALLELIC LOSS OF CHROMOSOME-16Q AND CHROMOSOME-10Q IN HUMAN PROSTATE-CANCER [J].
CARTER, BS ;
EWING, CM ;
WARD, WS ;
TREIGER, BF ;
AALDERS, TW ;
SCHALKEN, JA ;
EPSTEIN, JI ;
ISAACS, WB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (22) :8751-8755
[4]   COMPARATIVE GENOMIC HYBRIDIZATION, ALLELIC IMBALANCE, AND FLUORESCENCE IN-SITU HYBRIDIZATION ON CHROMOSOME-8 IN PROSTATE-CANCER [J].
CHER, ML ;
MACGROGAN, D ;
BOOKSTEIN, R ;
BROWN, JA ;
JENKINS, RB ;
JENSEN, RH .
GENES CHROMOSOMES & CANCER, 1994, 11 (03) :153-162
[5]  
Cher ML, 1996, CANCER RES, V56, P3091
[6]   THE DCC GENE - STRUCTURAL-ANALYSIS AND MUTATIONS IN COLORECTAL CARCINOMAS [J].
CHO, KR ;
OLINER, JD ;
SIMONS, JW ;
HEDRICK, L ;
FEARON, ER ;
PREISINGER, AC ;
HEDGE, P ;
SILVERMAN, GA ;
VOGELSTEIN, B .
GENOMICS, 1994, 19 (03) :525-531
[7]  
Cunningham JM, 1996, CANCER RES, V56, P4475
[8]   Nomenclature: Vertebrate mediators of TGF beta family signals [J].
Derynck, R ;
Gelbart, WM ;
Harland, RM ;
Heldin, CH ;
Kern, SE ;
Massague, J ;
Melton, DA ;
Mlodzik, MB ;
Padgett, RW ;
Roberts, AB ;
Smith, J ;
Thomsen, GH ;
Vogelstein, B ;
Wang, XF .
CELL, 1996, 87 (02) :173-173
[9]   MADR2 maps to 18q21 and encodes a TGF beta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma [J].
Eppert, K ;
Scherer, SW ;
Ozcelik, H ;
Pirone, R ;
Hoodless, P ;
Kim, H ;
Tsui, LC ;
Bapat, B ;
Gallinger, S ;
Andrulis, IL ;
Thomsen, GH ;
Wrana, JL ;
Attisano, L .
CELL, 1996, 86 (04) :543-552
[10]  
FYNAN TM, 1993, CRIT REV ONCOGENESIS, V4, P493