Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites

Abstract Metastasis is the major cause of death in breast cancer patients. Although previous large-scale analyses have identified frequently altered genes specific to metastatic breast cancer (MBC) compared with those in primary breast cancer (PBC), metastatic site-specific altered genes in MBC rema...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Soojin Cha, Esak Lee, Hong-Hee Won
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/15c8250377344d4db0926e1ffce1bed0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:15c8250377344d4db0926e1ffce1bed0
record_format	dspace
spelling	oai:doaj.org-article:15c8250377344d4db0926e1ffce1bed02021-12-02T16:08:12ZComprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites10.1038/s41523-021-00303-y2374-4677https://doaj.org/article/15c8250377344d4db0926e1ffce1bed02021-07-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00303-yhttps://doaj.org/toc/2374-4677Abstract Metastasis is the major cause of death in breast cancer patients. Although previous large-scale analyses have identified frequently altered genes specific to metastatic breast cancer (MBC) compared with those in primary breast cancer (PBC), metastatic site-specific altered genes in MBC remain largely uncharacterized. Moreover, large-scale analyses are required owing to the low expected frequency of such alterations, likely caused by tumor heterogeneity and late dissemination of breast cancer. To clarify MBC-specific genetic alterations, we integrated publicly available clinical and mutation data of 261 genes, including MBC drivers, from 4268 MBC and 5217 PBC patients from eight different cohorts. We performed meta-analyses and logistic regression analyses to identify MBC-enriched genetic alterations relative to those in PBC across 15 different metastatic site sets. We identified 11 genes that were more frequently altered in MBC samples from pan-metastatic sites, including four genes (SMARCA4, TSC2, ATRX, and AURKA) which were not identified previously. ARID2 mutations were enriched in treatment-naïve de novo and post-treatment MBC samples, compared with that in treatment-naïve PBC samples. In metastatic site-specific analyses, associations of ESR1 with liver metastasis and RICTOR with bone metastasis were significant, regardless of intrinsic subtypes. Among the 15 metastatic site sets, ESR1 mutations were enriched in the liver and depleted in the lymph nodes, whereas TP53 mutations showed an opposite trend. Seven potential MBC driver mutations showed similar preferential enrichment in specific metastatic sites. This large-scale study identified new MBC genetic alterations according to various metastatic sites and highlights their potential role in breast cancer organotropism.Soojin ChaEsak LeeHong-Hee WonNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Soojin Cha Esak Lee Hong-Hee Won Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites
description	Abstract Metastasis is the major cause of death in breast cancer patients. Although previous large-scale analyses have identified frequently altered genes specific to metastatic breast cancer (MBC) compared with those in primary breast cancer (PBC), metastatic site-specific altered genes in MBC remain largely uncharacterized. Moreover, large-scale analyses are required owing to the low expected frequency of such alterations, likely caused by tumor heterogeneity and late dissemination of breast cancer. To clarify MBC-specific genetic alterations, we integrated publicly available clinical and mutation data of 261 genes, including MBC drivers, from 4268 MBC and 5217 PBC patients from eight different cohorts. We performed meta-analyses and logistic regression analyses to identify MBC-enriched genetic alterations relative to those in PBC across 15 different metastatic site sets. We identified 11 genes that were more frequently altered in MBC samples from pan-metastatic sites, including four genes (SMARCA4, TSC2, ATRX, and AURKA) which were not identified previously. ARID2 mutations were enriched in treatment-naïve de novo and post-treatment MBC samples, compared with that in treatment-naïve PBC samples. In metastatic site-specific analyses, associations of ESR1 with liver metastasis and RICTOR with bone metastasis were significant, regardless of intrinsic subtypes. Among the 15 metastatic site sets, ESR1 mutations were enriched in the liver and depleted in the lymph nodes, whereas TP53 mutations showed an opposite trend. Seven potential MBC driver mutations showed similar preferential enrichment in specific metastatic sites. This large-scale study identified new MBC genetic alterations according to various metastatic sites and highlights their potential role in breast cancer organotropism.
format	article
author	Soojin Cha Esak Lee Hong-Hee Won
author_facet	Soojin Cha Esak Lee Hong-Hee Won
author_sort	Soojin Cha
title	Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites
title_short	Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites
title_full	Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites
title_fullStr	Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites
title_full_unstemmed	Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites
title_sort	comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/15c8250377344d4db0926e1ffce1bed0
work_keys_str_mv	AT soojincha comprehensivecharacterizationofdistinctgeneticalterationsinmetastaticbreastcanceracrossvariousmetastaticsites AT esaklee comprehensivecharacterizationofdistinctgeneticalterationsinmetastaticbreastcanceracrossvariousmetastaticsites AT hongheewon comprehensivecharacterizationofdistinctgeneticalterationsinmetastaticbreastcanceracrossvariousmetastaticsites
_version_	1718384578789376000

Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites

Ejemplares similares