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Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers

Despite the explosion in the numbers of cancer genomic studies, metastasis is still the major cause of cancer mortality. In breast cancer, approximately one-fifth of metastatic patients survive 5 years. Therefore, detecting the patients at a high risk of developing distant metastasis at first diagno...

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Autores principales: Lee, Ji-Hyun, Zhao, Xing-Ming, Yoon, Ina, Lee, Jin Young, Kwon, Nam Hoon, Wang, Yin-Ying, Lee, Kyung-Min, Lee, Min-Joo, Kim, Jisun, Moon, Hyeong-Gon, In, Yongho, Hao, Jin-Kao, Park, Kyung-Mii, Noh, Dong-Young, Han, Wonshik, Kim, Sunghoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004232/
https://www.ncbi.nlm.nih.gov/pubmed/27625789
http://dx.doi.org/10.1038/celldisc.2016.25
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author Lee, Ji-Hyun
Zhao, Xing-Ming
Yoon, Ina
Lee, Jin Young
Kwon, Nam Hoon
Wang, Yin-Ying
Lee, Kyung-Min
Lee, Min-Joo
Kim, Jisun
Moon, Hyeong-Gon
In, Yongho
Hao, Jin-Kao
Park, Kyung-Mii
Noh, Dong-Young
Han, Wonshik
Kim, Sunghoon
author_facet Lee, Ji-Hyun
Zhao, Xing-Ming
Yoon, Ina
Lee, Jin Young
Kwon, Nam Hoon
Wang, Yin-Ying
Lee, Kyung-Min
Lee, Min-Joo
Kim, Jisun
Moon, Hyeong-Gon
In, Yongho
Hao, Jin-Kao
Park, Kyung-Mii
Noh, Dong-Young
Han, Wonshik
Kim, Sunghoon
author_sort Lee, Ji-Hyun
collection PubMed
description Despite the explosion in the numbers of cancer genomic studies, metastasis is still the major cause of cancer mortality. In breast cancer, approximately one-fifth of metastatic patients survive 5 years. Therefore, detecting the patients at a high risk of developing distant metastasis at first diagnosis is critical for effective treatment strategy. We hereby present a novel systems biology approach to identify driver mutations escalating the risk of metastasis based on both exome and RNA sequencing of our collected 78 normal-paired breast cancers. Unlike driver mutations occurring commonly in cancers as reported in the literature, the mutations detected here are relatively rare mutations occurring in less than half metastatic samples. By supposing that the driver mutations should affect the metastasis gene signatures, we develop a novel computational pipeline to identify the driver mutations that affect transcription factors regulating metastasis gene signatures. We identify driver mutations in ADPGK, NUP93, PCGF6, PKP2 and SLC22A5, which are verified to enhance cancer cell migration and prompt metastasis with in vitro experiments. The discovered somatic mutations may be helpful for identifying patients who are likely to develop distant metastasis.
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spelling pubmed-50042322016-09-13 Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers Lee, Ji-Hyun Zhao, Xing-Ming Yoon, Ina Lee, Jin Young Kwon, Nam Hoon Wang, Yin-Ying Lee, Kyung-Min Lee, Min-Joo Kim, Jisun Moon, Hyeong-Gon In, Yongho Hao, Jin-Kao Park, Kyung-Mii Noh, Dong-Young Han, Wonshik Kim, Sunghoon Cell Discov Article Despite the explosion in the numbers of cancer genomic studies, metastasis is still the major cause of cancer mortality. In breast cancer, approximately one-fifth of metastatic patients survive 5 years. Therefore, detecting the patients at a high risk of developing distant metastasis at first diagnosis is critical for effective treatment strategy. We hereby present a novel systems biology approach to identify driver mutations escalating the risk of metastasis based on both exome and RNA sequencing of our collected 78 normal-paired breast cancers. Unlike driver mutations occurring commonly in cancers as reported in the literature, the mutations detected here are relatively rare mutations occurring in less than half metastatic samples. By supposing that the driver mutations should affect the metastasis gene signatures, we develop a novel computational pipeline to identify the driver mutations that affect transcription factors regulating metastasis gene signatures. We identify driver mutations in ADPGK, NUP93, PCGF6, PKP2 and SLC22A5, which are verified to enhance cancer cell migration and prompt metastasis with in vitro experiments. The discovered somatic mutations may be helpful for identifying patients who are likely to develop distant metastasis. Nature Publishing Group 2016-08-30 /pmc/articles/PMC5004232/ /pubmed/27625789 http://dx.doi.org/10.1038/celldisc.2016.25 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lee, Ji-Hyun
Zhao, Xing-Ming
Yoon, Ina
Lee, Jin Young
Kwon, Nam Hoon
Wang, Yin-Ying
Lee, Kyung-Min
Lee, Min-Joo
Kim, Jisun
Moon, Hyeong-Gon
In, Yongho
Hao, Jin-Kao
Park, Kyung-Mii
Noh, Dong-Young
Han, Wonshik
Kim, Sunghoon
Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers
title Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers
title_full Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers
title_fullStr Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers
title_full_unstemmed Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers
title_short Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers
title_sort integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004232/
https://www.ncbi.nlm.nih.gov/pubmed/27625789
http://dx.doi.org/10.1038/celldisc.2016.25
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