Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization.

Genetic changes leading to the development of prostate cancer and factors that underlie the clinical progression of the disease are poorly characterized. Here, we used comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes along all chromosomes in 31 primary and 9 recurrent uncultured prostate carcinomas. The aim of the study was to identify those chromosome regions that contain genes important for the development of prostate cancer and to identify genetic markers of tumor progression. CGH analysis indicated that 74% of primary prostate carcinoma showed DNA sequence copy number changes. Losses were 5 times more common than gains and most often involved 8p (32%), 13q (32%), 6q (22%), 16q (19%), 18q (19%), and 9p (16%). Allelic loss studies with 5 polymorphic microsatellite markers for 4 different chromosomes were done from 13 samples and showed a 76% concordance with CGH results. In local recurrences that developed during endocrine therapy, there were significantly more gains (P < 0.001) and losses (P < 0.05) of DNA sequences than in primary tumors, with gains of 8q (found in 89% of recurrences versus 6% of primary tumors), X (56% versus 0%), and 7 (56% versus 10%), as well as loss of 8p (78% versus 32%), being particularly often involved. In conclusion, our CGH results indicate that losses of several chromosomal regions are common genetic changes in primary tumors, suggesting that deletional inactivation of putative tumor suppressor genes in these chromosomal sites is likely to underlie development of prostate cancer. Furthermore, the pattern of genetic changes seen in recurrent tumors with the frequent gains of 7, 8q, and X suggests that the progression of prostate cancer and development of hormone-independent growth may have a distinct genetic basis. These chromosome aberrations may have diagnostic utility as markers of prostate cancer progression.

[1]  P. Malone,et al.  Prostate , 1995 .

[2]  J Piper,et al.  Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors , 1994, Genes, chromosomes & cancer.

[3]  E. Bergstralh,et al.  Aneuploidy and aneusomy of chromosome 7 detected by fluorescence in situ hybridization are markers of poor prognosis in prostate cancer. , 1994, Cancer research.

[4]  M R Speicher,et al.  Chromosomal gains and losses in uveal melanomas detected by comparative genomic hybridization. , 1994, Cancer research.

[5]  M. Skolnick,et al.  A cell cycle regulator potentially involved in genesis of many tumor types. , 1994, Science.

[6]  S. Brewster,et al.  Somatic allelic loss at the DCC, APC, nm23-H1 and p53 tumor suppressor gene loci in human prostatic carcinoma. , 1994, The Journal of urology.

[7]  D. Morton,et al.  Loss of heterozygosity of the retinoblastoma and adenomatous polyposis susceptibility gene loci and in chromosomes 10p, 10q and 16q in human prostate cancer. , 1994, British journal of urology.

[8]  I. Petersen,et al.  Mapping of multiple DNA gains and losses in primary small cell lung carcinomas by comparative genomic hybridization. , 1994, Cancer research.

[9]  J Piper,et al.  Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C. Croce,et al.  Suppression of tumorigenicity of breast cancer cells by microcell-mediated chromosome transfer: studies on chromosomes 6 and 11. , 1994, Cancer research.

[11]  P. Troncoso,et al.  Trisomy 7: A potential cytogenetic marker of human prostate cancer progression , 1994, Genes, chromosomes & cancer.

[12]  A. Jauch,et al.  Copyright ©) American Society for Investigative Pathology Comparative Genomic Hybridization of Human Malignant Gliomas Reveals Multiple Amplification Sites and Nonrandom Chromosomal Gains and Losses , 2022 .

[13]  P. Walsh,et al.  Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer. , 1993, Cancer research.

[14]  J. Ragoussis,et al.  Frequent loss of heterozygosity on chromosome 6 in human ovarian carcinoma. , 1993, British Journal of Cancer.

[15]  T. Visakorpi,et al.  New prognostic factors in prostatic carcinoma. , 1993, European urology.

[16]  M. Stearns,et al.  Prostate cancer: therapeutic, diagnostic, and basic studies. , 1992, Laboratory investigation; a journal of technical methods and pathology.

[17]  D. Pinkel,et al.  Comparative Genomic Hybridization for Molecular Cytogenetic Analysis of Solid Tumors , 2022 .

[18]  W. Cavenee,et al.  Accumulation of genetic defects during astrocytoma progression , 1992, Cancer.

[19]  A. Sandberg.  Chromosomal abnormalities and related events in prostate cancer. , 1992, Human pathology.

[20]  V. P. Collins,et al.  Allelotyping of human prostatic adenocarcinoma. , 1991, Genomics.

[21]  J. Trent,et al.  Loss of heterozygosity for loci on the long arm of chromosome 6 in human malignant melanoma. , 1991, Cancer research.

[22]  P L Pearson,et al.  Allelotype of human breast carcinoma: a second major site for loss of heterozygosity is on chromosome 6q. , 1991, Oncogene.

[23]  U. Bergerheim,et al.  Deletion mapping of chromosomes 8, 10, and 16 in human prostatic carcinoma , 1991, Genes, chromosomes & cancer.

[24]  R. deVere White,et al.  Activated ras alleles in human carcinoma of the prostate are rare. , 1991, Cancer research.

[25]  W. Isaacs,et al.  ras gene mutations in human prostate cancer. , 1990, Cancer research.

[26]  J M Trent,et al.  Tumorigenicity in human melanoma cell lines controlled by introduction of human chromosome 6. , 1990, Science.

[27]  J D Siegal,et al.  Enhanced expression of the c‐myc protooncogene in high‐grade human prostate cancers , 1988, The Prostate.