Gene methylation in pleural mesothelioma

Correlations with clinico-pathological features and patient's follow-up

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Methylation of tumor suppressor genes is among the most frequent alterations in patients with malignant pleural mesothelioma (MPM). The aim of this study was to analyze the promoter methylation status of four tumor suppressor genes, p15INK4B, p16INK4A, RASSF1A and NORE1A in MPM. Samples of 79 MPM patients were analyzed using a methylation-specific PCR method. Associations between methylation status, clinico-pathological parameters (including proliferation index) and overall survival (OS) were examined. The analysis documented methylation in 30 cases (38%). The methylation frequency for individual genes was 19% for p15INK4B (n = 15), 11.4% for p16INK4A (n = 9), 20.2% for RASSF1A (n = 16) and 5.1% for Nore1A (n = 4). In the whole series methylation was associated to an increased proliferation index (P = 0.05). In patients treated with extrapleural pneumonectomy, methylated MPM showed a trend to a poorer OS in comparison to unmethylated cases (median OS 16 months vs. 35 months, P = 0.06, HR = 2.01, 95% CI 0.95-4.30). In the overall population, methylation did not correlate to patient outcome but a trend to an improved survival was detectable in ummethylated MPM treated with extrapleural pneumonectomy. This result suggests the need to select homogeneously treated and staged patients with MPM to address whether their methylation profile may impact on patient's survival.

Original languageEnglish
Pages (from-to)369-376
Number of pages8
JournalLung Cancer
Volume59
Issue number3
DOIs
Publication statusPublished - Mar 2008

Fingerprint

Mesothelioma
Methylation
Genes
Survival
Pneumonectomy
Tumor Suppressor Genes
Gene Frequency
Malignant Mesothelioma
Polymerase Chain Reaction

Keywords

  • Clinico-pathological parameters
  • Extrapleural pneumonectomy
  • Mesothelioma
  • Methylation
  • Proliferation
  • Survival

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "Gene methylation in pleural mesothelioma: Correlations with clinico-pathological features and patient's follow-up",
abstract = "Methylation of tumor suppressor genes is among the most frequent alterations in patients with malignant pleural mesothelioma (MPM). The aim of this study was to analyze the promoter methylation status of four tumor suppressor genes, p15INK4B, p16INK4A, RASSF1A and NORE1A in MPM. Samples of 79 MPM patients were analyzed using a methylation-specific PCR method. Associations between methylation status, clinico-pathological parameters (including proliferation index) and overall survival (OS) were examined. The analysis documented methylation in 30 cases (38{\%}). The methylation frequency for individual genes was 19{\%} for p15INK4B (n = 15), 11.4{\%} for p16INK4A (n = 9), 20.2{\%} for RASSF1A (n = 16) and 5.1{\%} for Nore1A (n = 4). In the whole series methylation was associated to an increased proliferation index (P = 0.05). In patients treated with extrapleural pneumonectomy, methylated MPM showed a trend to a poorer OS in comparison to unmethylated cases (median OS 16 months vs. 35 months, P = 0.06, HR = 2.01, 95{\%} CI 0.95-4.30). In the overall population, methylation did not correlate to patient outcome but a trend to an improved survival was detectable in ummethylated MPM treated with extrapleural pneumonectomy. This result suggests the need to select homogeneously treated and staged patients with MPM to address whether their methylation profile may impact on patient's survival.",
keywords = "Clinico-pathological parameters, Extrapleural pneumonectomy, Mesothelioma, Methylation, Proliferation, Survival",
author = "Annarita Destro and Ceresoli, {Giovanni L.} and Ekaterina Baryshnikova and Isabella Garassino and Zucali, {Paolo A.} and {De Vincenzo}, Fabio and Paolo Bianchi and Emanuela Morenghi and Alberto Testori and Marco Alloisio and Armando Santoro and Massimo Roncalli",
year = "2008",
month = "3",
doi = "10.1016/j.lungcan.2007.08.035",
language = "English",
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pages = "369--376",
journal = "Lung Cancer",
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T1 - Gene methylation in pleural mesothelioma

T2 - Correlations with clinico-pathological features and patient's follow-up

AU - Destro, Annarita

AU - Ceresoli, Giovanni L.

AU - Baryshnikova, Ekaterina

AU - Garassino, Isabella

AU - Zucali, Paolo A.

AU - De Vincenzo, Fabio

AU - Bianchi, Paolo

AU - Morenghi, Emanuela

AU - Testori, Alberto

AU - Alloisio, Marco

AU - Santoro, Armando

AU - Roncalli, Massimo

PY - 2008/3

Y1 - 2008/3

N2 - Methylation of tumor suppressor genes is among the most frequent alterations in patients with malignant pleural mesothelioma (MPM). The aim of this study was to analyze the promoter methylation status of four tumor suppressor genes, p15INK4B, p16INK4A, RASSF1A and NORE1A in MPM. Samples of 79 MPM patients were analyzed using a methylation-specific PCR method. Associations between methylation status, clinico-pathological parameters (including proliferation index) and overall survival (OS) were examined. The analysis documented methylation in 30 cases (38%). The methylation frequency for individual genes was 19% for p15INK4B (n = 15), 11.4% for p16INK4A (n = 9), 20.2% for RASSF1A (n = 16) and 5.1% for Nore1A (n = 4). In the whole series methylation was associated to an increased proliferation index (P = 0.05). In patients treated with extrapleural pneumonectomy, methylated MPM showed a trend to a poorer OS in comparison to unmethylated cases (median OS 16 months vs. 35 months, P = 0.06, HR = 2.01, 95% CI 0.95-4.30). In the overall population, methylation did not correlate to patient outcome but a trend to an improved survival was detectable in ummethylated MPM treated with extrapleural pneumonectomy. This result suggests the need to select homogeneously treated and staged patients with MPM to address whether their methylation profile may impact on patient's survival.

AB - Methylation of tumor suppressor genes is among the most frequent alterations in patients with malignant pleural mesothelioma (MPM). The aim of this study was to analyze the promoter methylation status of four tumor suppressor genes, p15INK4B, p16INK4A, RASSF1A and NORE1A in MPM. Samples of 79 MPM patients were analyzed using a methylation-specific PCR method. Associations between methylation status, clinico-pathological parameters (including proliferation index) and overall survival (OS) were examined. The analysis documented methylation in 30 cases (38%). The methylation frequency for individual genes was 19% for p15INK4B (n = 15), 11.4% for p16INK4A (n = 9), 20.2% for RASSF1A (n = 16) and 5.1% for Nore1A (n = 4). In the whole series methylation was associated to an increased proliferation index (P = 0.05). In patients treated with extrapleural pneumonectomy, methylated MPM showed a trend to a poorer OS in comparison to unmethylated cases (median OS 16 months vs. 35 months, P = 0.06, HR = 2.01, 95% CI 0.95-4.30). In the overall population, methylation did not correlate to patient outcome but a trend to an improved survival was detectable in ummethylated MPM treated with extrapleural pneumonectomy. This result suggests the need to select homogeneously treated and staged patients with MPM to address whether their methylation profile may impact on patient's survival.

KW - Clinico-pathological parameters

KW - Extrapleural pneumonectomy

KW - Mesothelioma

KW - Methylation

KW - Proliferation

KW - Survival

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U2 - 10.1016/j.lungcan.2007.08.035

DO - 10.1016/j.lungcan.2007.08.035

M3 - Article

VL - 59

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EP - 376

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

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