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Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-e...

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Autores principales: Luo, Rui, Chong, Weelic, Wei, Qiang, Zhang, Zhenchao, Wang, Chun, Ye, Zhong, Abu-Khalaf, Maysa M., Silver, Daniel P., Stapp, Robert T., Jiang, Wei, Myers, Ronald E., Li, Bingshan, Cristofanilli, Massimo, Yang, Hushan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169683/
https://www.ncbi.nlm.nih.gov/pubmed/34075047
http://dx.doi.org/10.1038/s41523-021-00278-w
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author Luo, Rui
Chong, Weelic
Wei, Qiang
Zhang, Zhenchao
Wang, Chun
Ye, Zhong
Abu-Khalaf, Maysa M.
Silver, Daniel P.
Stapp, Robert T.
Jiang, Wei
Myers, Ronald E.
Li, Bingshan
Cristofanilli, Massimo
Yang, Hushan
author_facet Luo, Rui
Chong, Weelic
Wei, Qiang
Zhang, Zhenchao
Wang, Chun
Ye, Zhong
Abu-Khalaf, Maysa M.
Silver, Daniel P.
Stapp, Robert T.
Jiang, Wei
Myers, Ronald E.
Li, Bingshan
Cristofanilli, Massimo
Yang, Hushan
author_sort Luo, Rui
collection PubMed
description Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal structures to demonstrate ITH. Our results showed that KMT2C was the most frequently mutated gene (42%, 5/12 samples), followed by HECTD1, LAMA3, FLG2, UGT2B4, STK33, BRCA2, ACP4, PIK3CA, and DNAH8 (all nine genes tied at 33% frequency, 4/12 samples). Our data indicated that PTEN and FBXW7 mutations may be considered driver gene mutations for IBC. We identified various subclonal structures and different levels of ITH between IBC patients, and mutations in the genes EIF4G3, IL12RB2, and PDE4B may potentially generate ITH in IBC.
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spelling pubmed-81696832021-06-07 Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer Luo, Rui Chong, Weelic Wei, Qiang Zhang, Zhenchao Wang, Chun Ye, Zhong Abu-Khalaf, Maysa M. Silver, Daniel P. Stapp, Robert T. Jiang, Wei Myers, Ronald E. Li, Bingshan Cristofanilli, Massimo Yang, Hushan NPJ Breast Cancer Article Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal structures to demonstrate ITH. Our results showed that KMT2C was the most frequently mutated gene (42%, 5/12 samples), followed by HECTD1, LAMA3, FLG2, UGT2B4, STK33, BRCA2, ACP4, PIK3CA, and DNAH8 (all nine genes tied at 33% frequency, 4/12 samples). Our data indicated that PTEN and FBXW7 mutations may be considered driver gene mutations for IBC. We identified various subclonal structures and different levels of ITH between IBC patients, and mutations in the genes EIF4G3, IL12RB2, and PDE4B may potentially generate ITH in IBC. Nature Publishing Group UK 2021-06-01 /pmc/articles/PMC8169683/ /pubmed/34075047 http://dx.doi.org/10.1038/s41523-021-00278-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Luo, Rui
Chong, Weelic
Wei, Qiang
Zhang, Zhenchao
Wang, Chun
Ye, Zhong
Abu-Khalaf, Maysa M.
Silver, Daniel P.
Stapp, Robert T.
Jiang, Wei
Myers, Ronald E.
Li, Bingshan
Cristofanilli, Massimo
Yang, Hushan
Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer
title Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer
title_full Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer
title_fullStr Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer
title_full_unstemmed Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer
title_short Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer
title_sort whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169683/
https://www.ncbi.nlm.nih.gov/pubmed/34075047
http://dx.doi.org/10.1038/s41523-021-00278-w
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