Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative Tumors
Estrogen receptor (ER)-positive progesterone receptor (PR)-negative breast cancers are infrequent but clinically challenging. Despite the volume of genomic data available on these tumors, their biology remains poorly understood. Here, we aimed to identify clinically relevant subclasses of ER+/PR&...
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MDPI AG
2019-01-01
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author | Gianluca Lopez Jole Costanza Matteo Colleoni Laura Fontana Stefano Ferrero Monica Miozzo Nicola Fusco |
author_facet | Gianluca Lopez Jole Costanza Matteo Colleoni Laura Fontana Stefano Ferrero Monica Miozzo Nicola Fusco |
author_sort | Gianluca Lopez |
collection | DOAJ |
description | Estrogen receptor (ER)-positive progesterone receptor (PR)-negative breast cancers are infrequent but clinically challenging. Despite the volume of genomic data available on these tumors, their biology remains poorly understood. Here, we aimed to identify clinically relevant subclasses of ER+/PR− breast cancers based on their mutational landscape. The Cancer Genomics Data Server was interrogated for mutational and clinical data of all ER+ breast cancers with information on PR status from The Cancer Genome Atlas (TCGA), Memorial Sloan Kettering (MSK), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) projects. Clustering analysis was performed using gplots, ggplot2, and ComplexHeatmap packages. Comparisons between groups were performed using the Student’s t-test and the test of Equal or Given Proportions. Survival curves were built according to the Kaplan⁻Meier method; differences in survival were assessed with the log-rank test. A total of 3570 ER+ breast cancers (PR− n = 959, 27%; PR+ n = 2611, 73%) were analyzed. Mutations in well-known cancer genes such as <em>TP53</em>, <em>GATA3</em>, <em>CDH1</em>, <em>HER2</em>, <em>CDH1</em>, and <em>BRAF</em> were private to or enriched for in PR− tumors. Mutual exclusivity analysis revealed the presence of four molecular clusters with significantly different prognosis on the basis of <em>PIK3CA</em> and <em>TP53</em> status. ER+/PR− breast cancers are genetically heterogeneous and encompass a variety of distinct entities in terms of prognostic and predictive information. |
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spelling | doaj.art-110a10d7c6794353aa5760f1e77da4022022-12-22T02:56:05ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-01-0120351010.3390/ijms20030510ijms20030510Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative TumorsGianluca Lopez0Jole Costanza1Matteo Colleoni2Laura Fontana3Stefano Ferrero4Monica Miozzo5Nicola Fusco6Division of Pathology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, 20122 Milan, ItalyResearch Laboratory Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122, Milan, ItalyDivision of Pathology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, 20122 Milan, ItalyMedical Genetics, Department of Pathophysiology and Transplantation, University of Milan, 20122, Milan, ItalyDivision of Pathology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, 20122 Milan, ItalyResearch Laboratory Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122, Milan, ItalyDivision of Pathology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, 20122 Milan, ItalyEstrogen receptor (ER)-positive progesterone receptor (PR)-negative breast cancers are infrequent but clinically challenging. Despite the volume of genomic data available on these tumors, their biology remains poorly understood. Here, we aimed to identify clinically relevant subclasses of ER+/PR− breast cancers based on their mutational landscape. The Cancer Genomics Data Server was interrogated for mutational and clinical data of all ER+ breast cancers with information on PR status from The Cancer Genome Atlas (TCGA), Memorial Sloan Kettering (MSK), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) projects. Clustering analysis was performed using gplots, ggplot2, and ComplexHeatmap packages. Comparisons between groups were performed using the Student’s t-test and the test of Equal or Given Proportions. Survival curves were built according to the Kaplan⁻Meier method; differences in survival were assessed with the log-rank test. A total of 3570 ER+ breast cancers (PR− n = 959, 27%; PR+ n = 2611, 73%) were analyzed. Mutations in well-known cancer genes such as <em>TP53</em>, <em>GATA3</em>, <em>CDH1</em>, <em>HER2</em>, <em>CDH1</em>, and <em>BRAF</em> were private to or enriched for in PR− tumors. Mutual exclusivity analysis revealed the presence of four molecular clusters with significantly different prognosis on the basis of <em>PIK3CA</em> and <em>TP53</em> status. ER+/PR− breast cancers are genetically heterogeneous and encompass a variety of distinct entities in terms of prognostic and predictive information.https://www.mdpi.com/1422-0067/20/3/510breast cancerprogesterone receptor negativemutational profilingPI3K pathwayTP53 |
spellingShingle | Gianluca Lopez Jole Costanza Matteo Colleoni Laura Fontana Stefano Ferrero Monica Miozzo Nicola Fusco Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative Tumors International Journal of Molecular Sciences breast cancer progesterone receptor negative mutational profiling PI3K pathway TP53 |
title | Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative Tumors |
title_full | Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative Tumors |
title_fullStr | Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative Tumors |
title_full_unstemmed | Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative Tumors |
title_short | Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative Tumors |
title_sort | molecular insights into the classification of luminal breast cancers the genomic heterogeneity of progesterone negative tumors |
topic | breast cancer progesterone receptor negative mutational profiling PI3K pathway TP53 |
url | https://www.mdpi.com/1422-0067/20/3/510 |
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