Correlations between 06-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma

A prospective GICNO study

Alba A. Brandes, Alicia Tosoni, Giovanna Cavallo, Michele Reni, Enrico Franceschi, Laura Bonaldi, Roberta Bertorelle, Marina Gardiman, Claudio Ghimenton, Paolo Iuzzolino, Annalisa Pession, Valeria Blatt, Mario Ermani

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Purpose: To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, 06-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. Patients and Methods: From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1 p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. Results: The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1 p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1 p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1 p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). Conclusion: TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.

Original languageEnglish
Pages (from-to)4746-4753
Number of pages8
JournalJournal of Clinical Oncology
Volume24
Issue number29
DOIs
Publication statusPublished - Oct 10 2006

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temozolomide
Oligodendroglioma
Methyltransferases
Methylation
Prospective Studies
DNA
Loss of Heterozygosity
Survival
Monosomy 1p Chromosome 1
Chromosomes, Human, Pair 1
DNA Methylation
Fluorescence In Situ Hybridization

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Correlations between 06-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma : A prospective GICNO study. / Brandes, Alba A.; Tosoni, Alicia; Cavallo, Giovanna; Reni, Michele; Franceschi, Enrico; Bonaldi, Laura; Bertorelle, Roberta; Gardiman, Marina; Ghimenton, Claudio; Iuzzolino, Paolo; Pession, Annalisa; Blatt, Valeria; Ermani, Mario.

In: Journal of Clinical Oncology, Vol. 24, No. 29, 10.10.2006, p. 4746-4753.

Research output: Contribution to journalArticle

Brandes, Alba A. ; Tosoni, Alicia ; Cavallo, Giovanna ; Reni, Michele ; Franceschi, Enrico ; Bonaldi, Laura ; Bertorelle, Roberta ; Gardiman, Marina ; Ghimenton, Claudio ; Iuzzolino, Paolo ; Pession, Annalisa ; Blatt, Valeria ; Ermani, Mario. / Correlations between 06-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma : A prospective GICNO study. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 29. pp. 4746-4753.
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abstract = "Purpose: To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, 06-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. Patients and Methods: From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58{\%}) had AO and 28 patients (42{\%}) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1 p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. Results: The overall response rate was 46.3{\%} (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5{\%} v 25{\%}, P = .003). Combined 1 p/19q allelic loss was found in 32 patients (47.8{\%}), while MGMT methylation occurred in 37 (68.5{\%}) of 54 assessable patients. 1 p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1 p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). Conclusion: TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.",
author = "Brandes, {Alba A.} and Alicia Tosoni and Giovanna Cavallo and Michele Reni and Enrico Franceschi and Laura Bonaldi and Roberta Bertorelle and Marina Gardiman and Claudio Ghimenton and Paolo Iuzzolino and Annalisa Pession and Valeria Blatt and Mario Ermani",
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T1 - Correlations between 06-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma

T2 - A prospective GICNO study

AU - Brandes, Alba A.

AU - Tosoni, Alicia

AU - Cavallo, Giovanna

AU - Reni, Michele

AU - Franceschi, Enrico

AU - Bonaldi, Laura

AU - Bertorelle, Roberta

AU - Gardiman, Marina

AU - Ghimenton, Claudio

AU - Iuzzolino, Paolo

AU - Pession, Annalisa

AU - Blatt, Valeria

AU - Ermani, Mario

PY - 2006/10/10

Y1 - 2006/10/10

N2 - Purpose: To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, 06-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. Patients and Methods: From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1 p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. Results: The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1 p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1 p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1 p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). Conclusion: TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.

AB - Purpose: To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, 06-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. Patients and Methods: From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1 p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. Results: The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1 p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1 p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1 p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). Conclusion: TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.

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DO - 10.1200/JCO.2006.06.3891

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