Molecular disorders in transitional vs. peripheral zone prostate adenocarcinoma

Piergiuseppe Colombo, Carlo Patriarca, Rosa Maria Alfano, Barbara Cassani, Giorgia Ceva Grimaldi, Massimo Roncalli, Silvano Bosari, Guido Coggi, Biagio Campo, Victor E. Gould

Research output: Contribution to journalArticle

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Abstract

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been shown to be mechanisms for tumor-suppressor gene inactivation in human oncogenesis. In our study, we examined LOH and MSI using 16 polymorphic markers of DNA for chromosomes 1, 3, 7, 8, 10 and 11. Microdissected tumor samples were isolated from 32 patients, representing 11 foci of incidentally discovered prostate cancer of the transitional zone (TZ), 12 prostate cancer of the peripheral zone (PZ) and 10 of high-grade PIN. We found loss of heterozygosity in the TZ group in 91% of informative cases (10/11) with al least 1 marker compared to 58% of cases (7/12) in PZ group and 70% of cases (7/10) in the HGPIN group. Chromosome 7 showed the highest rate of allelic loss in all 3 categories, with loss of 43% of loci in PIN, 37% in TZ tumors and 3 1% in PZ tumors. At chromosome 1, t LOH was detected in 26% of loci in the TZ group, in 7% of loci in the PZ group and in 13% of loci in the PIN group. On chromosome 8, the PZ and HGPIN group showed allelic loss in 22% and 21% of loci, respectively, compared to 10% detected in the TZ group. The TZ group showed a significant higher rate of allelic instability compared to that observed in tumor samples from the peripheral zone: 73% of cases (8/11) showed genetic alterations (RER+ phenotype) in at least 4 loci analyzed compared to 8% and 10% in the PZ and HGPIN groups, respectively (p = 0.0006). These data suggest that transitional zone carcinoma and peripheral zone carcinoma display distinct and specific genetic alterations in different chromosomes. This diversity may help explain biologic and clinical differences between carcinomas arising in these distinct zones of the prostate. Also our results strongly suggest that the RER+ mutator phenotype could be linked to early development of transitional zone prostate carcinoma.

Original languageEnglish
Pages (from-to)383-389
Number of pages7
JournalInternational Journal of Cancer
Volume94
Issue number3
DOIs
Publication statusPublished - Nov 1 2001

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Loss of Heterozygosity
Prostate
Adenocarcinoma
Carcinoma
Microsatellite Instability
Chromosomes, Human, Pair 1
Neoplasms
Prostatic Neoplasms
Phenotype
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 3
Chromosomes, Human, Pair 7
Gene Silencing
Tumor Suppressor Genes
Genetic Markers
Carcinogenesis
Chromosomes

Keywords

  • Loss of heterozygosity
  • Microsatellite instability
  • Peripheral zone carcinoma
  • Prostate carcinoma
  • Transitional zone carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular disorders in transitional vs. peripheral zone prostate adenocarcinoma. / Colombo, Piergiuseppe; Patriarca, Carlo; Alfano, Rosa Maria; Cassani, Barbara; Grimaldi, Giorgia Ceva; Roncalli, Massimo; Bosari, Silvano; Coggi, Guido; Campo, Biagio; Gould, Victor E.

In: International Journal of Cancer, Vol. 94, No. 3, 01.11.2001, p. 383-389.

Research output: Contribution to journalArticle

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abstract = "Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been shown to be mechanisms for tumor-suppressor gene inactivation in human oncogenesis. In our study, we examined LOH and MSI using 16 polymorphic markers of DNA for chromosomes 1, 3, 7, 8, 10 and 11. Microdissected tumor samples were isolated from 32 patients, representing 11 foci of incidentally discovered prostate cancer of the transitional zone (TZ), 12 prostate cancer of the peripheral zone (PZ) and 10 of high-grade PIN. We found loss of heterozygosity in the TZ group in 91{\%} of informative cases (10/11) with al least 1 marker compared to 58{\%} of cases (7/12) in PZ group and 70{\%} of cases (7/10) in the HGPIN group. Chromosome 7 showed the highest rate of allelic loss in all 3 categories, with loss of 43{\%} of loci in PIN, 37{\%} in TZ tumors and 3 1{\%} in PZ tumors. At chromosome 1, t LOH was detected in 26{\%} of loci in the TZ group, in 7{\%} of loci in the PZ group and in 13{\%} of loci in the PIN group. On chromosome 8, the PZ and HGPIN group showed allelic loss in 22{\%} and 21{\%} of loci, respectively, compared to 10{\%} detected in the TZ group. The TZ group showed a significant higher rate of allelic instability compared to that observed in tumor samples from the peripheral zone: 73{\%} of cases (8/11) showed genetic alterations (RER+ phenotype) in at least 4 loci analyzed compared to 8{\%} and 10{\%} in the PZ and HGPIN groups, respectively (p = 0.0006). These data suggest that transitional zone carcinoma and peripheral zone carcinoma display distinct and specific genetic alterations in different chromosomes. This diversity may help explain biologic and clinical differences between carcinomas arising in these distinct zones of the prostate. Also our results strongly suggest that the RER+ mutator phenotype could be linked to early development of transitional zone prostate carcinoma.",
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AU - Patriarca, Carlo

AU - Alfano, Rosa Maria

AU - Cassani, Barbara

AU - Grimaldi, Giorgia Ceva

AU - Roncalli, Massimo

AU - Bosari, Silvano

AU - Coggi, Guido

AU - Campo, Biagio

AU - Gould, Victor E.

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AB - Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been shown to be mechanisms for tumor-suppressor gene inactivation in human oncogenesis. In our study, we examined LOH and MSI using 16 polymorphic markers of DNA for chromosomes 1, 3, 7, 8, 10 and 11. Microdissected tumor samples were isolated from 32 patients, representing 11 foci of incidentally discovered prostate cancer of the transitional zone (TZ), 12 prostate cancer of the peripheral zone (PZ) and 10 of high-grade PIN. We found loss of heterozygosity in the TZ group in 91% of informative cases (10/11) with al least 1 marker compared to 58% of cases (7/12) in PZ group and 70% of cases (7/10) in the HGPIN group. Chromosome 7 showed the highest rate of allelic loss in all 3 categories, with loss of 43% of loci in PIN, 37% in TZ tumors and 3 1% in PZ tumors. At chromosome 1, t LOH was detected in 26% of loci in the TZ group, in 7% of loci in the PZ group and in 13% of loci in the PIN group. On chromosome 8, the PZ and HGPIN group showed allelic loss in 22% and 21% of loci, respectively, compared to 10% detected in the TZ group. The TZ group showed a significant higher rate of allelic instability compared to that observed in tumor samples from the peripheral zone: 73% of cases (8/11) showed genetic alterations (RER+ phenotype) in at least 4 loci analyzed compared to 8% and 10% in the PZ and HGPIN groups, respectively (p = 0.0006). These data suggest that transitional zone carcinoma and peripheral zone carcinoma display distinct and specific genetic alterations in different chromosomes. This diversity may help explain biologic and clinical differences between carcinomas arising in these distinct zones of the prostate. Also our results strongly suggest that the RER+ mutator phenotype could be linked to early development of transitional zone prostate carcinoma.

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