Abstract 1835: Development of Mammary Hyperplasia, Dysplasia, and Invasive Ductal Carcinoma in Transgenic Mice Expressing the 8p11 Amplicon Oncogene NSD3 (WHSC1L1)

The study investigated the effects of overexpressing the oncogene NSD3 in the mammary glands of transgenic mice, which is linked to the 8p11-12 locus associated with poor breast cancer outcomes. The transgenic mice exhibited significant mammary gland abnormalities, including increased branching, terminal bud formation, and alveolar hyperplasia. These mice also showed a lactation defect, with underdeveloped pups displaying delayed hair growth and eye opening. By 40 weeks, many transgenic mice developed palpable tumors, which were similar to human breast cancer patterns, such as micropapillary and cribriform ductal carcinoma in situ. The findings suggested that NSD3 overexpression led to mammary gland deformation, inhibited functional differentiation, and tumor formation, highlighting the need for further research on NSD3's oncogenic role to improve outcomes in cancers with 8p11-12 alterations.