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Genetic Alterations of Triple Negative Breast Cancer By Targeted Next Generation Sequencing And Correlation With Tumor Morphology

Triple negative breast cancer represents a heterogeneous group of breast carcinomas, both at the histologic and genetic level. While recent molecular studies have comprehensively characterized the genetic landscape of these tumors, few have integrated a detailed histologic examination into the analy...

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Autores principales: Weisman, Paul S, Ng, Charlotte K.Y., Brogi, Edi, Eisenberg, Rachel E, Won, Helen H., Piscuoglio, Salvatore, De Filippo, Maria R., Ioris, Rafael, Akram, Muzaffar, Norton, Larry, Weigelt, Britta, Berger, Michael F., Reis-Filho, Jorge S., Wen, Hannah Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848211/
https://www.ncbi.nlm.nih.gov/pubmed/26939876
http://dx.doi.org/10.1038/modpathol.2016.39
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author Weisman, Paul S
Ng, Charlotte K.Y.
Brogi, Edi
Eisenberg, Rachel E
Won, Helen H.
Piscuoglio, Salvatore
De Filippo, Maria R.
Ioris, Rafael
Akram, Muzaffar
Norton, Larry
Weigelt, Britta
Berger, Michael F.
Reis-Filho, Jorge S.
Wen, Hannah Y.
author_facet Weisman, Paul S
Ng, Charlotte K.Y.
Brogi, Edi
Eisenberg, Rachel E
Won, Helen H.
Piscuoglio, Salvatore
De Filippo, Maria R.
Ioris, Rafael
Akram, Muzaffar
Norton, Larry
Weigelt, Britta
Berger, Michael F.
Reis-Filho, Jorge S.
Wen, Hannah Y.
author_sort Weisman, Paul S
collection PubMed
description Triple negative breast cancer represents a heterogeneous group of breast carcinomas, both at the histologic and genetic level. While recent molecular studies have comprehensively characterized the genetic landscape of these tumors, few have integrated a detailed histologic examination into the analysis. In this study, we defined the genetic alterations in 39 triple negative breast cancers using a high-depth targeted massively parallel sequencing assay and correlated the findings with a detailed morphologic analysis. We obtained representative frozen tissue of primary triple negative breast cancers from patients treated at our institution between 2002 and 2010. We characterized tumors according to their histologic subtype and morphologic features. DNA was extracted from paired frozen primary tumor and normal tissue samples and was subjected to a targeted massively parallel sequencing platform comprising 229 cancer associated genes common across all experiments. The average number of non-synonymous mutations was 3 (range 0–10) per case. The most frequent somatic alterations were mutations in TP53 (74%) and PIK3CA (10%) and MYC amplifications (26%). Triple negative breast cancers with apocrine differentiation less frequently harbored TP53 mutations (25%) and MYC gains (0%), and displayed a high mutation frequency in PIK3CA and other PI3K signaling pathway related genes (75%). Using a targeted massively parallel sequencing platform, we identified the key somatic genetic alterations previously reported in triple negative breast cancers. Furthermore, our findings show that triple negative breast cancers with apocrine differentiation constitute a distinct subset, characterized by a high frequency of PI3K pathway alterations similar to luminal subtypes of breast cancer.
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spelling pubmed-48482112016-09-04 Genetic Alterations of Triple Negative Breast Cancer By Targeted Next Generation Sequencing And Correlation With Tumor Morphology Weisman, Paul S Ng, Charlotte K.Y. Brogi, Edi Eisenberg, Rachel E Won, Helen H. Piscuoglio, Salvatore De Filippo, Maria R. Ioris, Rafael Akram, Muzaffar Norton, Larry Weigelt, Britta Berger, Michael F. Reis-Filho, Jorge S. Wen, Hannah Y. Mod Pathol Article Triple negative breast cancer represents a heterogeneous group of breast carcinomas, both at the histologic and genetic level. While recent molecular studies have comprehensively characterized the genetic landscape of these tumors, few have integrated a detailed histologic examination into the analysis. In this study, we defined the genetic alterations in 39 triple negative breast cancers using a high-depth targeted massively parallel sequencing assay and correlated the findings with a detailed morphologic analysis. We obtained representative frozen tissue of primary triple negative breast cancers from patients treated at our institution between 2002 and 2010. We characterized tumors according to their histologic subtype and morphologic features. DNA was extracted from paired frozen primary tumor and normal tissue samples and was subjected to a targeted massively parallel sequencing platform comprising 229 cancer associated genes common across all experiments. The average number of non-synonymous mutations was 3 (range 0–10) per case. The most frequent somatic alterations were mutations in TP53 (74%) and PIK3CA (10%) and MYC amplifications (26%). Triple negative breast cancers with apocrine differentiation less frequently harbored TP53 mutations (25%) and MYC gains (0%), and displayed a high mutation frequency in PIK3CA and other PI3K signaling pathway related genes (75%). Using a targeted massively parallel sequencing platform, we identified the key somatic genetic alterations previously reported in triple negative breast cancers. Furthermore, our findings show that triple negative breast cancers with apocrine differentiation constitute a distinct subset, characterized by a high frequency of PI3K pathway alterations similar to luminal subtypes of breast cancer. 2016-03-04 2016-05 /pmc/articles/PMC4848211/ /pubmed/26939876 http://dx.doi.org/10.1038/modpathol.2016.39 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Weisman, Paul S
Ng, Charlotte K.Y.
Brogi, Edi
Eisenberg, Rachel E
Won, Helen H.
Piscuoglio, Salvatore
De Filippo, Maria R.
Ioris, Rafael
Akram, Muzaffar
Norton, Larry
Weigelt, Britta
Berger, Michael F.
Reis-Filho, Jorge S.
Wen, Hannah Y.
Genetic Alterations of Triple Negative Breast Cancer By Targeted Next Generation Sequencing And Correlation With Tumor Morphology
title Genetic Alterations of Triple Negative Breast Cancer By Targeted Next Generation Sequencing And Correlation With Tumor Morphology
title_full Genetic Alterations of Triple Negative Breast Cancer By Targeted Next Generation Sequencing And Correlation With Tumor Morphology
title_fullStr Genetic Alterations of Triple Negative Breast Cancer By Targeted Next Generation Sequencing And Correlation With Tumor Morphology
title_full_unstemmed Genetic Alterations of Triple Negative Breast Cancer By Targeted Next Generation Sequencing And Correlation With Tumor Morphology
title_short Genetic Alterations of Triple Negative Breast Cancer By Targeted Next Generation Sequencing And Correlation With Tumor Morphology
title_sort genetic alterations of triple negative breast cancer by targeted next generation sequencing and correlation with tumor morphology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848211/
https://www.ncbi.nlm.nih.gov/pubmed/26939876
http://dx.doi.org/10.1038/modpathol.2016.39
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