Loss of heterozygosity of the retinoblastoma and adenomatous polyposis susceptibility gene loci and in chromosomes 10p, 10q and 16q in human prostate cancer.

OBJECTIVE To examine prostate tumours for losses of known or suspected tumour suppressor genes to determine some of the important events in the genesis of this common cancer. MATERIALS AND METHODS Paired tumour and blood samples were obtained from 21 patients who underwent transurethral resection of malignant prostate glands for urinary outflow obstruction. Paired tumour and normal tissue (leucocytes) DNA was extracted and examined for possible losses of several known or suspected tumour suppressor genes, using restriction fragment length polymorphism techniques to detect loss of heterozygosity. RESULTS Deletions of the retinoblastoma susceptibility gene (RB1) locus were found in six of nine informative cases using two intragenic probes (p68RS2.0 and p123m1.8). The locus related to the familial adenomatous polyposis susceptibility (APC) gene demonstrated loss of heterozygosity in three of seven informative cases using the EF5.44 probe. Losses were also noted in loci on chromosome 10p in four of 19 informative cases (probe cTBQ7), chromosome 10q in eight out of 19 informative cases (probes EFD75 and D10S90) and in 16q in three of 17 informative cases (probe D16S7). CONCLUSION These findings suggest that losses of the RB1 and APC tumour suppressor genes and suspected tumour suppressor genes on 10p, 10q and 16q may be important events in the genesis of prostatic tumours.

[1]  Bert Vogelstein,et al.  APC mutations occur early during colorectal tumorigenesis , 1992, Nature.

[2]  J. Neoptolemos,et al.  Predictive diagnosis of familial adenomatous polyposis with linked DNA markers: population based study. , 1992, BMJ.

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

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

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

[6]  G. H. Weiss,et al.  Molecular analysis of genetic changes in the origin and development of renal cell carcinoma. , 1991, Cancer research.

[7]  H. J. Evans,et al.  Linked DNA markers for presymptomatic diagnosis of familial adenomatous polyposis , 1991, The Lancet.

[8]  Y. Nakamura,et al.  Allelotype of renal cell carcinoma. , 1991, Cancer research.

[9]  D. Brachman,et al.  Two prostate carcinoma cell lines demonstrate abnormalities in tumor suppressor genes , 1991, Journal of surgical oncology.

[10]  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.

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

[12]  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.

[13]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[14]  S. Grimmond,et al.  Molecular biology of urological tumours. , 1990, British journal of urology.

[15]  Y. Miller,et al.  Lack of expression of aminoacylase-1 in small cell lung cancer. Evidence for inactivation of genes encoded by chromosome 3p. , 1989, The Journal of clinical investigation.

[16]  F. Mitelman,et al.  Multiple structural chromosome rearrangements, including del(7q) and del(10q), in an adenocarcinoma of the prostate. , 1988, Cancer genetics and cytogenetics.

[17]  Y. Nakamura,et al.  Genetic alterations during colorectal-tumor development. , 1988, The New England journal of medicine.

[18]  P. Nowell.  Mechanisms of tumor progression. , 1986, Cancer research.

[19]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[20]  Hutchison Gb.  Indications and surgical approaches for prostatic cancer. , 1981 .

[21]  E. Southern.  Detection of specific sequences among DNA fragments separated by gel electrophoresis. , 1975, Journal of molecular biology.

[22]  Roy G. Smith,et al.  Amplification, rearrangement, and elevated expression of c‐myc in the human prostatic carcinoma cell line LNCaP , 1989, The Prostate.

[23]  T. Stamey,et al.  Activated ki‐ras oncogene in human prostatic adenocarcinoma , 1987, The Prostate.

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

[25]  R. Matusik,et al.  Expression of the c-myc proto-oncogene in prostatic tissue. , 1987, Progress in clinical and biological research.