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Whole-exome analysis in osteosarcoma to identify a personalized therapy
Osteosarcoma is the most common pediatric primary non-hematopoietic bone tumor. Survival of these young patients is related to the response to chemotherapy and development of metastases. Despite many advances in cancer research, chemotherapy regimens for osteosarcoma are still based on non-selective...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655208/ https://www.ncbi.nlm.nih.gov/pubmed/29113313 http://dx.doi.org/10.18632/oncotarget.19010 |
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author | Chiappetta, Caterina Mancini, Massimiliano Lessi, Francesca Aretini, Paolo De Gregorio, Veronica Puggioni, Chiara Carletti, Raffaella Petrozza, Vincenzo Civita, Prospero Franceschi, Sara Naccarato, Antonio G. Rocca, Carlo Della Mazzanti, Chiara M. Di Cristofano, Claudio |
author_facet | Chiappetta, Caterina Mancini, Massimiliano Lessi, Francesca Aretini, Paolo De Gregorio, Veronica Puggioni, Chiara Carletti, Raffaella Petrozza, Vincenzo Civita, Prospero Franceschi, Sara Naccarato, Antonio G. Rocca, Carlo Della Mazzanti, Chiara M. Di Cristofano, Claudio |
author_sort | Chiappetta, Caterina |
collection | PubMed |
description | Osteosarcoma is the most common pediatric primary non-hematopoietic bone tumor. Survival of these young patients is related to the response to chemotherapy and development of metastases. Despite many advances in cancer research, chemotherapy regimens for osteosarcoma are still based on non-selective cytotoxic drugs. It is essential to investigate new specific molecular therapies for osteosarcoma to increase the survival rate of these patients. We performed exomic sequence analyses of 8 diagnostic biopsies of patients with conventional high grade osteosarcoma to advance our understanding of their genetic underpinnings and to correlate the genetic alteration with the clinical and pathological features of each patient to identify a personalized therapy. We identified 18,275 somatic variations in 8,247 genes and we found three mutated genes in 7/8 (87%) samples (KIF1B, NEB and KMT2C). KMT2C showed the highest number of variations; it is an important component of a histone H3 lysine 4 methyltransferase complex and it is one of the histone modifiers previously implicated in carcinogenesis, never studied in osteosarcoma. Moreover, we found a group of 15 genes that showed variations only in patients that did not respond to therapy and developed metastasis and some of these genes are involved in carcinogenesis and tumor progression in other tumors. These data could offer the opportunity to get a key molecular target to identify possible new strategies for early diagnosis and new therapeutic approaches for osteosarcoma and to provide a tailored treatment for each patient based on their genetic profile. |
format | Online Article Text |
id | pubmed-5655208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56552082017-11-06 Whole-exome analysis in osteosarcoma to identify a personalized therapy Chiappetta, Caterina Mancini, Massimiliano Lessi, Francesca Aretini, Paolo De Gregorio, Veronica Puggioni, Chiara Carletti, Raffaella Petrozza, Vincenzo Civita, Prospero Franceschi, Sara Naccarato, Antonio G. Rocca, Carlo Della Mazzanti, Chiara M. Di Cristofano, Claudio Oncotarget Research Paper Osteosarcoma is the most common pediatric primary non-hematopoietic bone tumor. Survival of these young patients is related to the response to chemotherapy and development of metastases. Despite many advances in cancer research, chemotherapy regimens for osteosarcoma are still based on non-selective cytotoxic drugs. It is essential to investigate new specific molecular therapies for osteosarcoma to increase the survival rate of these patients. We performed exomic sequence analyses of 8 diagnostic biopsies of patients with conventional high grade osteosarcoma to advance our understanding of their genetic underpinnings and to correlate the genetic alteration with the clinical and pathological features of each patient to identify a personalized therapy. We identified 18,275 somatic variations in 8,247 genes and we found three mutated genes in 7/8 (87%) samples (KIF1B, NEB and KMT2C). KMT2C showed the highest number of variations; it is an important component of a histone H3 lysine 4 methyltransferase complex and it is one of the histone modifiers previously implicated in carcinogenesis, never studied in osteosarcoma. Moreover, we found a group of 15 genes that showed variations only in patients that did not respond to therapy and developed metastasis and some of these genes are involved in carcinogenesis and tumor progression in other tumors. These data could offer the opportunity to get a key molecular target to identify possible new strategies for early diagnosis and new therapeutic approaches for osteosarcoma and to provide a tailored treatment for each patient based on their genetic profile. Impact Journals LLC 2017-07-05 /pmc/articles/PMC5655208/ /pubmed/29113313 http://dx.doi.org/10.18632/oncotarget.19010 Text en Copyright: © 2017 Chiappetta et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Chiappetta, Caterina Mancini, Massimiliano Lessi, Francesca Aretini, Paolo De Gregorio, Veronica Puggioni, Chiara Carletti, Raffaella Petrozza, Vincenzo Civita, Prospero Franceschi, Sara Naccarato, Antonio G. Rocca, Carlo Della Mazzanti, Chiara M. Di Cristofano, Claudio Whole-exome analysis in osteosarcoma to identify a personalized therapy |
title | Whole-exome analysis in osteosarcoma to identify a personalized therapy |
title_full | Whole-exome analysis in osteosarcoma to identify a personalized therapy |
title_fullStr | Whole-exome analysis in osteosarcoma to identify a personalized therapy |
title_full_unstemmed | Whole-exome analysis in osteosarcoma to identify a personalized therapy |
title_short | Whole-exome analysis in osteosarcoma to identify a personalized therapy |
title_sort | whole-exome analysis in osteosarcoma to identify a personalized therapy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655208/ https://www.ncbi.nlm.nih.gov/pubmed/29113313 http://dx.doi.org/10.18632/oncotarget.19010 |
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