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Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets

BACKGROUND: Several studies have investigated the molecular drivers and therapeutic targets in adult soft tissue sarcomas. However, such studies are limited by the genomic heterogeneity and rarity of sarcomas, particularly in those with complex and unbalanced karyotypes. Additional biomarkers are ne...

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Autores principales: Kim, Jihyun, Kim, June Hyuk, Kang, Hyun Guy, Park, Seog Yun, Yu, Jung Yeon, Lee, Eun Young, Oh, Sung Eun, Kim, Young Ho, Yun, Tak, Park, Charny, Cho, Soo Young, You, Hye Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311917/
https://www.ncbi.nlm.nih.gov/pubmed/30598078
http://dx.doi.org/10.1186/s12881-018-0722-6
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author Kim, Jihyun
Kim, June Hyuk
Kang, Hyun Guy
Park, Seog Yun
Yu, Jung Yeon
Lee, Eun Young
Oh, Sung Eun
Kim, Young Ho
Yun, Tak
Park, Charny
Cho, Soo Young
You, Hye Jin
author_facet Kim, Jihyun
Kim, June Hyuk
Kang, Hyun Guy
Park, Seog Yun
Yu, Jung Yeon
Lee, Eun Young
Oh, Sung Eun
Kim, Young Ho
Yun, Tak
Park, Charny
Cho, Soo Young
You, Hye Jin
author_sort Kim, Jihyun
collection PubMed
description BACKGROUND: Several studies have investigated the molecular drivers and therapeutic targets in adult soft tissue sarcomas. However, such studies are limited by the genomic heterogeneity and rarity of sarcomas, particularly in those with complex and unbalanced karyotypes. Additional biomarkers are needed across sarcoma types to improve therapeutic strategies. To investigate the molecular characteristics of complex karyotype sarcomas (CKSs) for therapeutic targets, we performed genomic profiling. RESULTS: The mutational landscape showed that TP53, ATRX, and PTEN genes were highly mutated. CKS samples were categorized into three groups based on copy number variations that were associated with CDK4 and RB1 signatures. Integrated analysis of genomic and transcriptomic data revealed several pathways related to PDGFR, which could be a strategic target for anti-sarcoma therapy. CONCLUSIONS: This study provides a detailed molecular classification of CKSs and proposes several therapeutic targets. Targeted or combinational therapies for treating CKS should be considered before chemotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0722-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-63119172019-01-07 Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets Kim, Jihyun Kim, June Hyuk Kang, Hyun Guy Park, Seog Yun Yu, Jung Yeon Lee, Eun Young Oh, Sung Eun Kim, Young Ho Yun, Tak Park, Charny Cho, Soo Young You, Hye Jin BMC Med Genet Research BACKGROUND: Several studies have investigated the molecular drivers and therapeutic targets in adult soft tissue sarcomas. However, such studies are limited by the genomic heterogeneity and rarity of sarcomas, particularly in those with complex and unbalanced karyotypes. Additional biomarkers are needed across sarcoma types to improve therapeutic strategies. To investigate the molecular characteristics of complex karyotype sarcomas (CKSs) for therapeutic targets, we performed genomic profiling. RESULTS: The mutational landscape showed that TP53, ATRX, and PTEN genes were highly mutated. CKS samples were categorized into three groups based on copy number variations that were associated with CDK4 and RB1 signatures. Integrated analysis of genomic and transcriptomic data revealed several pathways related to PDGFR, which could be a strategic target for anti-sarcoma therapy. CONCLUSIONS: This study provides a detailed molecular classification of CKSs and proposes several therapeutic targets. Targeted or combinational therapies for treating CKS should be considered before chemotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0722-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-31 /pmc/articles/PMC6311917/ /pubmed/30598078 http://dx.doi.org/10.1186/s12881-018-0722-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kim, Jihyun
Kim, June Hyuk
Kang, Hyun Guy
Park, Seog Yun
Yu, Jung Yeon
Lee, Eun Young
Oh, Sung Eun
Kim, Young Ho
Yun, Tak
Park, Charny
Cho, Soo Young
You, Hye Jin
Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets
title Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets
title_full Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets
title_fullStr Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets
title_full_unstemmed Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets
title_short Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets
title_sort integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311917/
https://www.ncbi.nlm.nih.gov/pubmed/30598078
http://dx.doi.org/10.1186/s12881-018-0722-6
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