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.

Differential expression profile of mRNAs, lncRNAs, and circRNAs reveals potential molecular mechanism in breast cancer

“…RNA sequencing, which can be applied to identify the tumor driver genes, not only brought incredible changes and advantages in the field of tumor [ 17–19 ], but expands understanding and provides potential treatment strategies for some special types of tumors, such as inflammatory breast cancer and juvenile papillomatosis with co-existing breast carcinoma [ 20 , 21 ]. In our study, we found 3764 DE mRNAs, 5416 DE lncRNAs, and 148 DE circRNAs by RNA sequencing in three breast cancer tissues compared with their paired normal tissues.…”

Juvenile Papillomatosis of Breast

“…2 Another recent study identified clonal somatic PIK3CA hotspot mutations in 2 of 3 cases of juvenile papillomatosis, including 1 with an associated ductal carcinoma in situ and invasive ductal carcinoma. 3 Interestingly, the in situ and invasive carcinomas and the juvenile papillomatosis had a somatic clonal PIK3CA E542K hotspot mutation. 3…”

“…3 Interestingly, the in situ and invasive carcinomas and the juvenile papillomatosis had a somatic clonal PIK3CA E542K hotspot mutation. 3…”