Molecular Features of Aggressive Preinvasive Lesions driven by Combined MYC Activation and PTEN Loss in Mouse Prostate

Gain of MYC combined with biallelic PTEN loss strongly predicts prostate cancer mortality. Prior studies have shown that combined MYC overexpression and Pten loss resulted in the development of mouse prostatic intraepithelial neoplastic (PIN) precursor lesions that progress to invasive and metastatic disease (BMPC mice). Yet, single gene alterations in these mice result only in PIN. Herein, we performed transcriptomic profiling of PIN lesions from mouse prostates with MYC overexpression, loss of Pten, and the combination thereof in BMPC mice. Overall design: Mouse prostates harboring PIN lesions were dissected from mice engineered to have MYC activation alone (MYC PIN, ventral lobes), Pten loss alone(PTENloss PIN, anterior lobes), and the combination thereof (BMPC PIN, anterior lobes), as well as invasive primary adenocarcinomas and metastatic lesions from BMPC mice (BMPC Primary and BMPC Met) and wild-type controls from FVB anterior and ventral prostate lobes (FVB Anterior and FVB Ventral).