Genetic alterations in untreated metastases and androgen-independent prostate cancer detected by comparative genomic hybridization and allelotyping.

A newly developed method of comparative genomic hybridization (CGH) employing quantitative statistical comparisons was applied to DNA from two different types of advanced prostate cancer tissue. Multiple CGH analyses were obtained for each chromosome in each tumor, and the results of point-by-point comparison of the mean tumor:normal color ratio to a control normal:normal color ratio in each of 1247 evenly distributed data channels constituting the entire human genome were interpreted as loss, gain, or no change in copy number in the tumor genome. Group I tissue was obtained from prostate cancer metastases from 20 patients, 19 of whom had received no prior prostate cancer treatment. This DNA also was analyzed by Southern and microsatellite allelotyping at 53 different loci on 20 different chromosome arms. CGH results agreed with allelotyping results at 92% of the informative loci studied. These samples, which contained highly enriched tumor DNA, showed the highest rates of alteration yet reported in several chromosomal regions known to be altered frequently in prostate cancer: 8q gain (85%), 8p loss (80%), 13q loss (75%), 16q loss (55%), 17p loss (50%), and 10q loss (50%). Group II tissue was obtained predominately from primary or recurrent tumor from 11 patients who had been treated with long-term androgen-deprivation therapy and developed androgen-independent metastatic disease. Quantitative CGH analysis on DNA from these tissues showed chromosomal alterations that were very similar to those found in group I, suggesting that untreated metastatic tumors contain the bulk of chromosomal alterations necessary for recurrence to occur during androgen deprivation. In the entire data set, a number of previously undetected regions of frequent loss or gain were identified, including losses of chromosomes 2q (42%), 5q (39%), 6q (39%), and 15q (39%) and gains of chromosomes 11p (52%), 1q (52%), 3q (52%), and 2p (45%). Chi-squared analysis showed a significantly higher frequency of gain of the 4q25-q28 region in tumors from African-American patients, indicating a possible oncogene whose activation may play a role in the higher rate of progression seen in this ethnic group. Additional study of these frequently altered regions may provide insight into the mechanism of prostate cancer progression and lead to important tools for tumor-specific prognosis and therapy.

[1]  J. Gray,et al.  A t-statistic for objective interpretation of comparative genomic hybridization (CGH) profiles. , 1997, Cytometry.

[2]  Y. Nakamura,et al.  Localization of a tumor suppressor gene associated with progression of human prostate cancer within a 1.2 Mb region of 8p22‐p21.3 , 1995, Genes, chromosomes & cancer.

[3]  Jorma Isola,et al.  In vivo amplification of the androgen receptor gene and progression of human prostate cancer , 1995, Nature Genetics.

[4]  T. Visakorpi,et al.  Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization. , 1995, Cancer research.

[5]  J. Brooks,et al.  Allelic loss of the retinoblastoma gene in primary human prostatic adenocarcinomas , 1995, The Prostate.

[6]  K. Pienta,et al.  Effect of age and race on the survival of men with prostate cancer in the Metropolitan Detroit tricounty area, 1973 to 1987. , 1995, Urology.

[7]  P. Carroll,et al.  Mapping of regions of physical deletion on chromosome 16q in prostate cancer cells by fluorescence in situ hybridization (FISH). , 1995, The Journal of urology.

[8]  M. Bittner,et al.  DNA sequence amplification in human prostate cancer identified by chromosome microdissection: potential prognostic implications. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[9]  O. Cussenot,et al.  Genetic alterations in localized prostate cancer: Identification of a common region of deletion on chromosome arm 18q , 1994, Genes, chromosomes & cancer.

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

[11]  Z. F. Liu,et al.  Allelic loss of chromosome 18q and prognosis in colorectal cancer. , 1994, The New England journal of medicine.

[12]  W. Isaacs,et al.  Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. , 1994, Cancer research.

[13]  D. Bostwick,et al.  Loss of chromosome arm 8p loci in prostate cancer: Mapping by quantitative allelic imbalance , 1994, Genes, chromosomes & cancer.

[14]  D. Grignon,et al.  Allelic loss in locally metastatic, multisampled prostate cancer. , 1994, Cancer research.

[15]  Y Kubota,et al.  Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas. , 1994, Cancer research.

[16]  N. Breslow,et al.  Loss of Heterozygosity for Chromosomes 16q and Ip in Wilms' Tumors Predicts an Adverse Outcome' , 2022 .

[17]  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.

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

[19]  Y. Furukawa,et al.  Structure, expression and chromosome assignment of the human catenin (cadherin-associated protein) alpha 1 gene (CTNNA1). , 1994, Cytogenetics and cell genetics.

[20]  P. Rabinovitch,et al.  Deletion mapping of chromosome 8p in colorectal carcinoma and dysplasia arising in ulcerative colitis, prostatic carcinoma, and malignant fibrous histiocytomas. , 1994, American Journal of Pathology.

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

[22]  W. Isaacs,et al.  Reduction of E-Cadherin Levels and Deletion of the α-Catenin Gene in Human Prostate Cancer Cells , 1993 .

[23]  S. Hilsenbeck,et al.  p53 is mutated in a subset of advanced-stage prostate cancers. , 1993, Cancer research.

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

[25]  G. Gyapay,et al.  A second-generation linkage map of the human genome , 1992, Nature.

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

[27]  W. Isaacs,et al.  Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. , 1991, Cancer research.

[28]  N E Morton,et al.  Parameters of the human genome. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

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

[30]  W. Isaacs,et al.  Allelic loss of chromosomes 16q and 10q in human prostate cancer. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[31]  W. Lee,et al.  Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Ankita Patel,et al.  Frequency and pattern of karyotypic abnormalities in human prostate cancer. , 1990, Cancer research.

[33]  D. Ledbetter,et al.  Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. , 1989, Science.

[34]  J W Gray,et al.  Centromeric index versus DNA content flow karyotypes of human chromosomes measured by means of slit-scan flow cytometry. , 1987, Cytometry.

[35]  M. Melamed,et al.  Flow cytometry of prostate cancer: relationship of DNA content to survival. , 1987, Cancer research.

[36]  Stephen H. Friend,et al.  A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma , 1986, Nature.

[37]  Gleason Df.  Classification of prostatic carcinomas. , 1966 .

[38]  Jacob Cohen.  A Coefficient of Agreement for Nominal Scales , 1960 .