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Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma
Juvenile papillomatosis (JP) of the breast is a rare benign mass‐forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family hi...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869928/ https://www.ncbi.nlm.nih.gov/pubmed/33263939 http://dx.doi.org/10.1002/cjp2.190 |
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author | D'Alfonso, Timothy M Pareja, Fresia Da Cruz Paula, Arnaud Vahdatinia, Mahsa Gazzo, Andrea Ferrando, Lorenzo da Silva, Edaise M Cheng, Esther Sclafani, Lisa Chandarlapaty, Sarat Zhang, Hong Hoda, Syed A Wen, Hannah Y Brogi, Edi Weigelt, Britta Reis‐Filho, Jorge S |
author_facet | D'Alfonso, Timothy M Pareja, Fresia Da Cruz Paula, Arnaud Vahdatinia, Mahsa Gazzo, Andrea Ferrando, Lorenzo da Silva, Edaise M Cheng, Esther Sclafani, Lisa Chandarlapaty, Sarat Zhang, Hong Hoda, Syed A Wen, Hannah Y Brogi, Edi Weigelt, Britta Reis‐Filho, Jorge S |
author_sort | D'Alfonso, Timothy M |
collection | PubMed |
description | Juvenile papillomatosis (JP) of the breast is a rare benign mass‐forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole‐exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC‐NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC‐NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC‐NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)‐positive breast cancers. We observed JP to harbor a dominant aging‐related mutational signature, whereas coexisting DCIS and IDC‐NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop. |
format | Online Article Text |
id | pubmed-7869928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78699282021-02-17 Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma D'Alfonso, Timothy M Pareja, Fresia Da Cruz Paula, Arnaud Vahdatinia, Mahsa Gazzo, Andrea Ferrando, Lorenzo da Silva, Edaise M Cheng, Esther Sclafani, Lisa Chandarlapaty, Sarat Zhang, Hong Hoda, Syed A Wen, Hannah Y Brogi, Edi Weigelt, Britta Reis‐Filho, Jorge S J Pathol Clin Res Brief Report Juvenile papillomatosis (JP) of the breast is a rare benign mass‐forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole‐exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC‐NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC‐NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC‐NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)‐positive breast cancers. We observed JP to harbor a dominant aging‐related mutational signature, whereas coexisting DCIS and IDC‐NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop. John Wiley & Sons, Inc. 2020-12-02 /pmc/articles/PMC7869928/ /pubmed/33263939 http://dx.doi.org/10.1002/cjp2.190 Text en © 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Brief Report D'Alfonso, Timothy M Pareja, Fresia Da Cruz Paula, Arnaud Vahdatinia, Mahsa Gazzo, Andrea Ferrando, Lorenzo da Silva, Edaise M Cheng, Esther Sclafani, Lisa Chandarlapaty, Sarat Zhang, Hong Hoda, Syed A Wen, Hannah Y Brogi, Edi Weigelt, Britta Reis‐Filho, Jorge S Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma |
title |
Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma |
title_full |
Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma |
title_fullStr |
Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma |
title_full_unstemmed |
Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma |
title_short |
Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma |
title_sort | whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869928/ https://www.ncbi.nlm.nih.gov/pubmed/33263939 http://dx.doi.org/10.1002/cjp2.190 |
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