P2-25-1 - The Correlation Between Rb1 Loss Signatures Derived From Mouse and Breast Cancers Equipped with Clinical Information

Abstract

Background: Inactivation of Retinoblastoma 1 (RB1) gene product is implicated in progression of breast, prostate and many other cancers. It has been shown that RB1 expression level is correlated with the subtypes and sensitivity to treatment in breast cancers. However, directly linking RB1 status to clinical behaviors in cancers has been hampered by heterogeneity in human cancers. To clarify the mechanism by which RB1 inactivation affects clinical courses, we obtained the gene expression profile by Rb1 depletion under genetically homogeneous conditions, and analyzed the correlation between Rb1 loss signatures and clinical behaviors in breast cancers.Methods: Trp53-null mouse derived tumor cells were transduced with shRNA of either control or Rb1, and whole RNA sequencing was performed. We compared the average between control samples and Rb1 knockdown samples. We extracted differentially expressed genes, and obtained Rb1 loss signatures by using homologous genes. Based on these signatures, we performed KEGG and GO analyses, detected overlapping genes using Mammaprit, OncotypeDX, and other reported breast cancer signatures. Also we investigated relevance to subtype, treatment sensitivity, and prognosis of breast cancer.Results: Some genes were found to be overlapped in Rb1 loss signatures and previously reported breast cancer signatures. Also the genes affected by Rb1 knockdown were included in signatures featuring high grade and poor prognosis in breast cancer. Conclusion:Rb1 depletion itself may associate clinical course in breast cancer.