Cargando…
Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family
Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221420/ https://www.ncbi.nlm.nih.gov/pubmed/27713419 http://dx.doi.org/10.1038/modpathol.2016.161 |
_version_ | 1782492804808704000 |
---|---|
author | Geyer, Felipe C Berman, Samuel H. Marchiò, Caterina Burke, Kathleen A Guerini-Rocco, Elena Piscuoglio, Salvatore Ng, Charlotte K Y Pareja, Fresia Wen, Hannah Y Hodi, Zoltan Schnitt, Stuart J Rakha, Emad A Ellis, Ian O Norton, Larry Weigelt, Britta Reis-Filho, Jorge S |
author_facet | Geyer, Felipe C Berman, Samuel H. Marchiò, Caterina Burke, Kathleen A Guerini-Rocco, Elena Piscuoglio, Salvatore Ng, Charlotte K Y Pareja, Fresia Wen, Hannah Y Hodi, Zoltan Schnitt, Stuart J Rakha, Emad A Ellis, Ian O Norton, Larry Weigelt, Britta Reis-Filho, Jorge S |
author_sort | Geyer, Felipe C |
collection | PubMed |
description | Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/deletions and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1–13) and 4.0 (1–7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12, or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions harboring frequent TP53 somatic mutations, and likely represent low-grade forms of triple-negative disease with no/minimal metastatic potential, of which a subset has the potential to progress to high-grade triple-negative breast cancer. |
format | Online Article Text |
id | pubmed-5221420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-52214202017-04-07 Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family Geyer, Felipe C Berman, Samuel H. Marchiò, Caterina Burke, Kathleen A Guerini-Rocco, Elena Piscuoglio, Salvatore Ng, Charlotte K Y Pareja, Fresia Wen, Hannah Y Hodi, Zoltan Schnitt, Stuart J Rakha, Emad A Ellis, Ian O Norton, Larry Weigelt, Britta Reis-Filho, Jorge S Mod Pathol Article Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/deletions and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1–13) and 4.0 (1–7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12, or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions harboring frequent TP53 somatic mutations, and likely represent low-grade forms of triple-negative disease with no/minimal metastatic potential, of which a subset has the potential to progress to high-grade triple-negative breast cancer. 2016-10-07 2017-01 /pmc/articles/PMC5221420/ /pubmed/27713419 http://dx.doi.org/10.1038/modpathol.2016.161 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 Geyer, Felipe C Berman, Samuel H. Marchiò, Caterina Burke, Kathleen A Guerini-Rocco, Elena Piscuoglio, Salvatore Ng, Charlotte K Y Pareja, Fresia Wen, Hannah Y Hodi, Zoltan Schnitt, Stuart J Rakha, Emad A Ellis, Ian O Norton, Larry Weigelt, Britta Reis-Filho, Jorge S Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family |
title | Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family |
title_full | Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family |
title_fullStr | Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family |
title_full_unstemmed | Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family |
title_short | Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family |
title_sort | genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221420/ https://www.ncbi.nlm.nih.gov/pubmed/27713419 http://dx.doi.org/10.1038/modpathol.2016.161 |
work_keys_str_mv | AT geyerfelipec geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT bermansamuelh geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT marchiocaterina geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT burkekathleena geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT gueriniroccoelena geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT piscuogliosalvatore geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT ngcharlotteky geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT parejafresia geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT wenhannahy geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT hodizoltan geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT schnittstuartj geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT rakhaemada geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT ellisiano geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT nortonlarry geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT weigeltbritta geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily AT reisfilhojorges geneticanalysisofmicroglandularadenosisandaciniccellcarcinomasofthebreastprovidesevidencefortheexistenceofalowgradetriplenegativebreastneoplasiafamily |