Intraductal papillomas (IDP) are challenging breast findings because of their variable risk of progression to malignancy. The molecular events driving IDP development and genomic features of malignant progression are poorly understood. In this study, genome-wide CNA and/or targeted mutation analysis was performed on 44 cases of IDP, of which 20 cases had coexisting ductal carcinoma in situ (DCIS), papillary DCIS or invasive ductal carcinoma (IDC). CNA were rare in pure IDP, but 69% carried an activating PIK3CA mutation. Among the synchronous IDP cases, 55% (11/20) were clonally related to the synchronous DCIS and/or IDC, only one of which had papillary histology. In contrast to pure IDP, PIK3CA mutations were absent from clonal cases. CNAs in any of chromosomes 1, 16 or 11 were significantly enriched in clonal IDP lesions compared to pure and non-clonal IDP. The observation that 55% of IDP are clonal to DCIS/IDC indicates that IDP can be a direct precursor for breast carcinoma, not limited to the papillary type. The absence of PIK3CA mutations and presence of CNAs in IDP could be used clinically to identify patients at high risk of progression to carcinoma.

导管内乳头状瘤 (IDP) 是一种具有挑战性的乳腺发现，因为它们进展为恶性肿瘤的风险各不相同。驱动 IDP 发展的分子事件和恶性进展的基因组特征知之甚少。本研究对44例IDP进行全基因组CNA和/或靶向突变分析，其中20例同时存在导管原位癌（DCIS）、乳头状DCIS或浸润性导管癌（IDC）。 CNA 在纯 IDP 中很少见，但 69% 携带激活PIK3CA突变。在同步IDP病例中，55%（11/20）与同步DCIS和/或IDC克隆相关，其中只有1例具有乳头状组织学。与纯 IDP 相比，克隆病例中不存在PIK3CA突变。与纯 IDP 和非克隆 IDP 相比，1、16 或 11 号染色体中任何一条的 CNA 在克隆 IDP 损伤中显着富集。 55%的IDP克隆至DCIS/IDC的观察结果表明，IDP可以是乳腺癌的直接前兆，而不仅限于乳头状型。 IDP 中不存在PIK3CA突变且存在 CNA 的情况可在临床上用于识别进展为癌症的高风险患者。