Abstract 1417: Expression of BARD1δ induces genetic instability and is associated with cervical carcinogenesis

Cervical cancer is always linked to infection with the human papilloma virus (HPV), which causes hyper-proliferation of cervical epithelial cells and neoplasia and cervical cancer. The viral oncoprotein interaction with host tumor suppressor proteins partially explains the uncontrolled proliferation, which ultimately progresses to cervical cancer. However, little is known about the specific factors that promote or inhibit the malignant transformation. Since a portion of HPV infections never evolves into cancer, the identification of discriminatory factors would be an important step towards the development of prognostic and therapeutic tools. Based on this notion, we investigated whether an isoform of BARD1, BARD1δ, which we found frequently expressed in cancer cells, plays a role in the malignant transformation of cervical epithelial cells. Using immunohystochemistry staining on tissue sections and RT-PCR we found that BARD1δ is expressed in proliferating cervical cancer cells, while normal BARD1 is repressed. BARD1 might be a driver of carcinogenesis and might be a critical event in the progression from hyper-proliferating cervical epithelium after HPV infection to cervical cancer. Together, our results show that an isoform of BARD1, BARD1δ, is increasingly expressed in precancerous stages of cervical cancer and the specific inhibition of BARD1δ may represent a novel approach for therapeutic interventions to prevent cervical carcinogenesis after HPV infection. Citation Format: Maxim Pilyugin, Pierre-Alain Andre, Nicole Concin, Gerda Hofstetter, Irmgard Irminger-Finger. Expression of BARD1δ induces genetic instability and is associated with cervical carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1417. doi:10.1158/1538-7445.AM2017-1417