Open AccessWhole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma
Author(s) -
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,
ReisFilho Jorge S
Publication year - 2021
Publication title -
the journal of pathology: clinical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.849
H-Index - 21
ISSN - 2056-4538
DOI - 10.1002/cjp2.190
Subject(s) - ductal carcinoma , exome sequencing , biology , pathology , breast cancer , germline mutation , papillomatosis , carcinoma , papilloma , cancer research , medicine , mutation , cancer , genetics , gene
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.