Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets

Akira Hirasawa, Fumiko Saito-Ohara, Jun Inoue, Daisuke Aoki, Nobuyuki Susumu, Tetsuji Yokoyama, Shiro Nozawa, Johji Inazawa, Issei Imoto

Research output: Contribution to journalArticle

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Abstract

Purpose: Although tumor stage is considered a prognostic feature for ovarian clear cell adenocarcinomas (OC-CAs), it is not likely to fully account for the clinical and biological variability characteristic of the disease. The aim of this study was to investigate aberrations of DNA copy number in OCCA tumors and identify genetic markers that would increase our understanding of the pathogenesis of OCCA and assist in more accurately predicting the outcome for an individual patient with this disease. Experimental Design: We determined copy number aberrations among 20 primary OCCA tumors by means of comparative genomic hybridization and investigated their relationship to clinicopathological data. We also measured expression levels of candidate target genes within critical regions by quantitative real-time reverse transcription-PCRs and compared those data with copy number status and patient outcomes. Results: We identified several nonrandom chromosomal aberrations among the 20 primary OCCA tumors examined. Among them, gain of DNA at 17q21-q24 showed significantly negative correlation with disease-free and over-all survival (P = 0.0012 and 0.0039, respectively, log-rank test). This correlation held even for patients with stage I tumors. Among 15 candidate genes within the 17q21-q24 region, we found significantly elevated expression of PPM1D and APPBP2, and their heightened expression correlated negatively with disease-free survival (P = 0.0090, log-rank test adjusted for multiple comparisons). Conclusions: Information gained from our relatively large panel of OCCA tumors suggested that 17q21-q24 gain and consequent overexpression of two potential targets, PPM1D and APPBP2, are associated with malignant phenotypes of this tumor and may be useful predictors for prognosis.

Original languageEnglish
Pages (from-to)1995-2004
Number of pages10
JournalClinical Cancer Research
Volume9
Issue number6
Publication statusPublished - 2003 Jun 1

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Clear Cell Adenocarcinoma
Neoplasms
Comparative Genomic Hybridization
DNA
Genetic Markers
Chromosome Aberrations
Genes
Reverse Transcription
Disease-Free Survival
Research Design
Phenotype
Polymerase Chain Reaction
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets. / Hirasawa, Akira; Saito-Ohara, Fumiko; Inoue, Jun; Aoki, Daisuke; Susumu, Nobuyuki; Yokoyama, Tetsuji; Nozawa, Shiro; Inazawa, Johji; Imoto, Issei.

In: Clinical Cancer Research, Vol. 9, No. 6, 01.06.2003, p. 1995-2004.

Research output: Contribution to journalArticle

Hirasawa, A, Saito-Ohara, F, Inoue, J, Aoki, D, Susumu, N, Yokoyama, T, Nozawa, S, Inazawa, J & Imoto, I 2003, 'Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets', Clinical Cancer Research, vol. 9, no. 6, pp. 1995-2004.
Hirasawa, Akira ; Saito-Ohara, Fumiko ; Inoue, Jun ; Aoki, Daisuke ; Susumu, Nobuyuki ; Yokoyama, Tetsuji ; Nozawa, Shiro ; Inazawa, Johji ; Imoto, Issei. / Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 6. pp. 1995-2004.
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AU - Hirasawa, Akira

AU - Saito-Ohara, Fumiko

AU - Inoue, Jun

AU - Aoki, Daisuke

AU - Susumu, Nobuyuki

AU - Yokoyama, Tetsuji

AU - Nozawa, Shiro

AU - Inazawa, Johji

AU - Imoto, Issei

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N2 - Purpose: Although tumor stage is considered a prognostic feature for ovarian clear cell adenocarcinomas (OC-CAs), it is not likely to fully account for the clinical and biological variability characteristic of the disease. The aim of this study was to investigate aberrations of DNA copy number in OCCA tumors and identify genetic markers that would increase our understanding of the pathogenesis of OCCA and assist in more accurately predicting the outcome for an individual patient with this disease. Experimental Design: We determined copy number aberrations among 20 primary OCCA tumors by means of comparative genomic hybridization and investigated their relationship to clinicopathological data. We also measured expression levels of candidate target genes within critical regions by quantitative real-time reverse transcription-PCRs and compared those data with copy number status and patient outcomes. Results: We identified several nonrandom chromosomal aberrations among the 20 primary OCCA tumors examined. Among them, gain of DNA at 17q21-q24 showed significantly negative correlation with disease-free and over-all survival (P = 0.0012 and 0.0039, respectively, log-rank test). This correlation held even for patients with stage I tumors. Among 15 candidate genes within the 17q21-q24 region, we found significantly elevated expression of PPM1D and APPBP2, and their heightened expression correlated negatively with disease-free survival (P = 0.0090, log-rank test adjusted for multiple comparisons). Conclusions: Information gained from our relatively large panel of OCCA tumors suggested that 17q21-q24 gain and consequent overexpression of two potential targets, PPM1D and APPBP2, are associated with malignant phenotypes of this tumor and may be useful predictors for prognosis.

AB - Purpose: Although tumor stage is considered a prognostic feature for ovarian clear cell adenocarcinomas (OC-CAs), it is not likely to fully account for the clinical and biological variability characteristic of the disease. The aim of this study was to investigate aberrations of DNA copy number in OCCA tumors and identify genetic markers that would increase our understanding of the pathogenesis of OCCA and assist in more accurately predicting the outcome for an individual patient with this disease. Experimental Design: We determined copy number aberrations among 20 primary OCCA tumors by means of comparative genomic hybridization and investigated their relationship to clinicopathological data. We also measured expression levels of candidate target genes within critical regions by quantitative real-time reverse transcription-PCRs and compared those data with copy number status and patient outcomes. Results: We identified several nonrandom chromosomal aberrations among the 20 primary OCCA tumors examined. Among them, gain of DNA at 17q21-q24 showed significantly negative correlation with disease-free and over-all survival (P = 0.0012 and 0.0039, respectively, log-rank test). This correlation held even for patients with stage I tumors. Among 15 candidate genes within the 17q21-q24 region, we found significantly elevated expression of PPM1D and APPBP2, and their heightened expression correlated negatively with disease-free survival (P = 0.0090, log-rank test adjusted for multiple comparisons). Conclusions: Information gained from our relatively large panel of OCCA tumors suggested that 17q21-q24 gain and consequent overexpression of two potential targets, PPM1D and APPBP2, are associated with malignant phenotypes of this tumor and may be useful predictors for prognosis.

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