Synapse - Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma

Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma Journal Article

Authors:	D'Alfonso, T. M.; Pareja, F.; Da Cruz Paula, A.; Vahdatinia, M.; Gazzo, A.; Ferrando, L.; da Silva, E. M.; Cheng, E.; Sclafani, L.; Chandarlapaty, S.; Zhang, H.; Hoda, S. A.; Wen, H. Y.; Brogi, E.; Weigelt, B.; Reis-Filho, J. S.
Article Title:	Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma
Abstract:	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. © 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.
Keywords:	breast carcinoma; pik3ca; juvenile papillomatosis
Journal Title:	Journal of Pathology: Clinical Research
Volume:	7
Issue:	2
ISSN:	2056-4538
Publisher:	Wiley Blackwell
Date Published:	2021-03-01
Start Page:	113
End Page:	120
Language:	English
DOI:	10.1002/cjp2.190
PUBMED:	33263939
PROVIDER:	scopus
PMCID:	PMC7869928
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85096976532&doi=10.1002%2fcjp2.190&partnerID=40&md5=c8b29c3702b5b070fb1fa361cad82b91
Notes:	Article -- Export Date: 1 March 2021 -- Source: Scopus