Molecular profiling basal 2 subtypes of triple-negative breast cancer cells and their response to histone deacetylase inhibitor

Abstract Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that often strikes young women, particularly minority women in their reproductive years. This cancer has a poor prognosis, mainly due to the lack of effective chemotherapeutic agents. Triple negative breast cancers present an additional problem, in that a histologically subtype can have molecularly different forms. Studies have shown that histological designated tumors yield different treatment results. Recently, molecular profiling of a patient’s tumor yielded detection of specific driver genes that resulted in the use of single or combination therapies targeting these driver genes. Basal 2 subtype is one of the most aggressive form of TNBC. This study examined the molecular profiles of two Basal 2 triple negative breast cancers representing two different African American women in response to treatment with vorinostat. Using a RT2 Profiler PCR gene expression array, vorinostat up-regulated 54 genes and downregulated 3 genes in HCC70 TNBC. In HCC1806 TNBC, 23 genes were upregulated and 38 downregulated. The most significant change in gene expression noted in HCC70 was in CCND2, which is hypermethylated in TNBC. Changes were also noted in SNA12, SERPINE, and TWIST. In HCC1806, significant changes in gene expression were noted in ABCB1, CCND2, CDKN1C and MMP9. These results clearly demonstrated that there is a differential response to a potential anti-tumor drug by different molecular subtypes. Up-regulation of CCND2 was observed in both basal 2 cell lines. CCND2 encodes cyclin D2 in which low expression is associated with poor prognosis. Understanding individual differences in cancer driver genes will greatly improve personalized medicine in TNBC. Citation Format: Beverly Lyn-Cook, Destiny Stovall, Beverly Word, Ebony Cotton, George Hammons. Molecular profiling basal 2 subtypes of triple-negative breast cancer cells and their response to histone deacetylase inhibitor [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B125.