Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer.

Allelic loss studies have been instrumental in identifying tumor suppressor gene loci in a variety of cancers. In this study we analyzed prostate cancer specimens from 52 patients for allelic loss using 8 polymorphic probes for the short arm of chromosome 8. Overall, 32 of 51 (63%) informative tumors showed loss of at least one locus on chromosome 8p. The most frequently deleted region is observed at chromosome 8p22-8p21.2. Loss of one allele is identified in 14 of 23 (61%) tumors at D8S163, in 15 of 32 (47%) tumors at lipoprotein lipase, and in 20 of 29 (69%) tumors at MSR, all on 8p22. Loss of one allele is identified in 16 of 27 (59%) tumors at D8S220 at 8p21.3-8p21.2. In addition to frequent loss of one allele at the MSR locus, one metastatic prostate cancer sample demonstrated homozygous deletion of MSR sequences. Loci telomeric and centromeric to this region are largely retained. A chromosome 8p deletion map is constructed and defines the smallest region of overlap to a 14-cM interval at 8p22 between D8S163 and lipoprotein lipase, flanking the MSR locus. Evidence of chromosome 8q multiplication at locus D8S39 was detected in 5 of 32 (16%) tumors, all of which demonstrated loss with at least one probe on chromosome 8p. This study extends the previous finding of frequent loss of chromosome 8p in prostate cancer by defining a common region of loss of heterozygosity at 8p22 and a homozygous deletion of the MSR locus contained within this region. This is the first homozygous deletion identified in the genome of a human prostate cancer and the highest rate of loss yet reported on chromosome 8p in cancer. These results strongly suggest the presence of a tumor suppressor gene in this region which is frequently inactivated in prostate cancer.

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

[2]  P. Lichter,et al.  Human clusterin (CLI) maps to 8p21 in proximity to the lipoprotein lipase (LPL) gene. , 1993, Genomics.

[3]  A. Wyllie,et al.  Deletion mapping in colorectal cancer of a putative tumour suppressor gene in 8p22-p21.3. , 1993, Oncogene.

[4]  M. Knowles,et al.  Deletion mapping of chromosome 8 in cancers of the urinary bladder using restriction fragment length polymorphisms and microsatellite polymorphisms. , 1993, Oncogene.

[5]  J. Epstein,et al.  Methods of radical prostatectomy specimen processing: a novel technique for harvesting fresh prostate cancer tissue and review of processing techniques. , 1993, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[6]  Y. Nakamura,et al.  A primary genetic linkage map of 14 polymorphic loci for the short arm of human chromosome 8. , 1993, Genomics.

[7]  Y. Nakamura,et al.  Evidence for the presence of two tumor suppressor genes on chromosome 8p for colorectal carcinoma. , 1993, Cancer research.

[8]  Y. Nakamura,et al.  Frequent multiplication of the long arm of chromosome 8 in hepatocellular carcinoma. , 1993, Cancer research.

[9]  T. Tong,et al.  Cancer statistics, 1993 , 1993, CA: a cancer journal for clinicians.

[10]  Y. Nakamura,et al.  Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular carcinoma, colorectal cancer, and lung cancer. , 1992, Cancer research.

[11]  M. Freeman,et al.  Rabbit aortic smooth muscle cells express inducible macrophage scavenger receptor messenger RNA that is absent from endothelial cells. , 1992, The Journal of clinical investigation.

[12]  S. Daiger,et al.  Human chromosome 8 linkage map based on short tandem repeat polymorphisms: effect of genotyping errors. , 1992, Genomics.

[13]  T. Visakorpi,et al.  Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation. , 1992, Journal of the National Cancer Institute.

[14]  F. Schröder,et al.  The TNM classification of prostate cancer , 1992, The Prostate. Supplement.

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

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

[17]  H. Aburatani,et al.  Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[18]  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.

[19]  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.

[20]  Kathleen R. Cho,et al.  Identification of a chromosome 18q gene that is altered in colorectal cancers. , 1990, Science.

[21]  Y. Nakamura,et al.  Allelotype of colorectal carcinomas. , 1989, Science.

[22]  R. Nussbaum,et al.  Report of the committee on the genetic constitution of the X chromosome. , 1988, Cytogenetics and cell genetics.

[23]  T. Kodama,et al.  Purification and characterization of a bovine acetyl low density lipoprotein receptor. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[24]  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.

[25]  T. Mohandas,et al.  Human genes involved in lipolysis of plasma lipoproteins: mapping of loci for lipoprotein lipase to 8p22 and hepatic lipase to 15q21. , 1987, Genomics.

[26]  B. Vogelstein,et al.  Prevalence of ras gene mutations in human colorectal cancers , 1987, Nature.

[27]  A. Sandberg,et al.  Chromosome rearrangements in a metastatic adenocarcinoma of the prostate. , 1985, Cancer genetics and cytogenetics.

[28]  K. Burton.  [105] Determination of DNA concentration with diphenylamine , 1968 .

[29]  J. Bailar,et al.  The histology and prognosis of prostatic cancer. , 1967, The Journal of urology.