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An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients
BACKGROUND: The molecular characteristics associated with the response to treatment in glioblastomas (GBMs) remain largely unknown. We performed a retrospective study to assess the genomic characteristics associated with the response of GBMs to either first-line chemotherapy or radiation therapy. Th...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944185/ https://www.ncbi.nlm.nih.gov/pubmed/20822523 http://dx.doi.org/10.1186/1476-4598-9-234 |
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author | Ducray, François de Reyniès, Aurélien Chinot, Olivier Idbaih, Ahmed Figarella-Branger, Dominique Colin, Carole Karayan-Tapon, Lucie Chneiweiss, Hervé Wager, Michel Vallette, François Marie, Yannick Rickman, David Thomas, Emilie Delattre, Jean-Yves Honnorat, Jérôme Sanson, Marc Berger, François |
author_facet | Ducray, François de Reyniès, Aurélien Chinot, Olivier Idbaih, Ahmed Figarella-Branger, Dominique Colin, Carole Karayan-Tapon, Lucie Chneiweiss, Hervé Wager, Michel Vallette, François Marie, Yannick Rickman, David Thomas, Emilie Delattre, Jean-Yves Honnorat, Jérôme Sanson, Marc Berger, François |
author_sort | Ducray, François |
collection | PubMed |
description | BACKGROUND: The molecular characteristics associated with the response to treatment in glioblastomas (GBMs) remain largely unknown. We performed a retrospective study to assess the genomic characteristics associated with the response of GBMs to either first-line chemotherapy or radiation therapy. The gene expression (n = 56) and genomic profiles (n = 67) of responders and non-responders to first-line chemotherapy or radiation therapy alone were compared on Affymetrix Plus 2 gene expression arrays and BAC CGH arrays. RESULTS: According to Verhaak et al.'s classification system, mesenchymal GBMs were more likely to respond to radiotherapy than to first-line chemotherapy, whereas classical GBMs were more likely to respond to first-line chemotherapy than to radiotherapy. In patients treated with radiation therapy alone, the response was associated with differential expression of microenvironment-associated genes; the expression of hypoxia-related genes was associated with short-term progression-free survival (< 5 months), whereas the expression of immune genes was associated with prolonged progression-free survival (> 10 months). Consistently, infiltration of the tumor by both CD3 and CD68 cells was significantly more frequent in responders to radiotherapy than in non-responders. In patients treated with first-line chemotherapy, the expression of stem-cell genes was associated with resistance to chemotherapy, and there was a significant association between response to treatment and p16 locus deletions. Consistently, in an independent data set of patients treated with either radiotherapy alone or with both radiotherapy and adjuvant chemotherapy, we found that patients with the p16 deletion benefited from adjuvant chemotherapy regardless of their MGMT promoter methylation status, whereas in patients without the p16 deletion, this benefit was only observed in patients with a methylated MGMT promoter. CONCLUSION: Differential expression of microenvironment genes and p16 locus deletion are associated with responses to radiation therapy and to first-line chemotherapy, respectively, in GBM. Recently identified transcriptomic subgroups of GBMs seem to respond differently to radiotherapy and to first-line chemotherapy. |
format | Text |
id | pubmed-2944185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29441852010-09-24 An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients Ducray, François de Reyniès, Aurélien Chinot, Olivier Idbaih, Ahmed Figarella-Branger, Dominique Colin, Carole Karayan-Tapon, Lucie Chneiweiss, Hervé Wager, Michel Vallette, François Marie, Yannick Rickman, David Thomas, Emilie Delattre, Jean-Yves Honnorat, Jérôme Sanson, Marc Berger, François Mol Cancer Research BACKGROUND: The molecular characteristics associated with the response to treatment in glioblastomas (GBMs) remain largely unknown. We performed a retrospective study to assess the genomic characteristics associated with the response of GBMs to either first-line chemotherapy or radiation therapy. The gene expression (n = 56) and genomic profiles (n = 67) of responders and non-responders to first-line chemotherapy or radiation therapy alone were compared on Affymetrix Plus 2 gene expression arrays and BAC CGH arrays. RESULTS: According to Verhaak et al.'s classification system, mesenchymal GBMs were more likely to respond to radiotherapy than to first-line chemotherapy, whereas classical GBMs were more likely to respond to first-line chemotherapy than to radiotherapy. In patients treated with radiation therapy alone, the response was associated with differential expression of microenvironment-associated genes; the expression of hypoxia-related genes was associated with short-term progression-free survival (< 5 months), whereas the expression of immune genes was associated with prolonged progression-free survival (> 10 months). Consistently, infiltration of the tumor by both CD3 and CD68 cells was significantly more frequent in responders to radiotherapy than in non-responders. In patients treated with first-line chemotherapy, the expression of stem-cell genes was associated with resistance to chemotherapy, and there was a significant association between response to treatment and p16 locus deletions. Consistently, in an independent data set of patients treated with either radiotherapy alone or with both radiotherapy and adjuvant chemotherapy, we found that patients with the p16 deletion benefited from adjuvant chemotherapy regardless of their MGMT promoter methylation status, whereas in patients without the p16 deletion, this benefit was only observed in patients with a methylated MGMT promoter. CONCLUSION: Differential expression of microenvironment genes and p16 locus deletion are associated with responses to radiation therapy and to first-line chemotherapy, respectively, in GBM. Recently identified transcriptomic subgroups of GBMs seem to respond differently to radiotherapy and to first-line chemotherapy. BioMed Central 2010-09-07 /pmc/articles/PMC2944185/ /pubmed/20822523 http://dx.doi.org/10.1186/1476-4598-9-234 Text en Copyright ©2010 Ducray et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Ducray, François de Reyniès, Aurélien Chinot, Olivier Idbaih, Ahmed Figarella-Branger, Dominique Colin, Carole Karayan-Tapon, Lucie Chneiweiss, Hervé Wager, Michel Vallette, François Marie, Yannick Rickman, David Thomas, Emilie Delattre, Jean-Yves Honnorat, Jérôme Sanson, Marc Berger, François An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients |
title | An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients |
title_full | An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients |
title_fullStr | An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients |
title_full_unstemmed | An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients |
title_short | An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients |
title_sort | anocef genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944185/ https://www.ncbi.nlm.nih.gov/pubmed/20822523 http://dx.doi.org/10.1186/1476-4598-9-234 |
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