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Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas
BACKGROUND: Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770569/ https://www.ncbi.nlm.nih.gov/pubmed/19835627 http://dx.doi.org/10.1186/1471-2407-9-368 |
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author | Österberg, Lovisa Levan, Kristina Partheen, Karolina Delle, Ulla Olsson, Björn Sundfeldt, Karin Horvath, György |
author_facet | Österberg, Lovisa Levan, Kristina Partheen, Karolina Delle, Ulla Olsson, Björn Sundfeldt, Karin Horvath, György |
author_sort | Österberg, Lovisa |
collection | PubMed |
description | BACKGROUND: Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers. METHODS: To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH), we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1) plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR) to evaluate the impact of DNA alterations on the transcriptional level. RESULTS: We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group. CONCLUSION: In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate these findings in an independent ovarian tumor series. |
format | Text |
id | pubmed-2770569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-27705692009-10-30 Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas Österberg, Lovisa Levan, Kristina Partheen, Karolina Delle, Ulla Olsson, Björn Sundfeldt, Karin Horvath, György BMC Cancer Research Article BACKGROUND: Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers. METHODS: To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH), we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1) plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR) to evaluate the impact of DNA alterations on the transcriptional level. RESULTS: We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group. CONCLUSION: In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate these findings in an independent ovarian tumor series. BioMed Central 2009-10-18 /pmc/articles/PMC2770569/ /pubmed/19835627 http://dx.doi.org/10.1186/1471-2407-9-368 Text en Copyright ©2009 Österberg 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 Article Österberg, Lovisa Levan, Kristina Partheen, Karolina Delle, Ulla Olsson, Björn Sundfeldt, Karin Horvath, György Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas |
title | Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas |
title_full | Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas |
title_fullStr | Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas |
title_full_unstemmed | Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas |
title_short | Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas |
title_sort | potential predictive markers of chemotherapy resistance in stage iii ovarian serous carcinomas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770569/ https://www.ncbi.nlm.nih.gov/pubmed/19835627 http://dx.doi.org/10.1186/1471-2407-9-368 |
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