Identification of CSNK1D and KLK6 as two common upregulated genes present in BRCA1 mutated triple-negative breast cancer and ovarian epithelial carcinoma.

Abstract

Deficiency in the breast cancer type 1 (BRCA1) gene expression predisposes to triple-negative breast cancer (TNBC) and ovarian cancer (OC). We previously identified by Comparative Genomic Hybridization (CGH) array a gain in the 17q25.3 genomic region in 90% of the BRCA1 mutated TNBC tissues, where 17 genes were up-regulated. A second region (Chr19_45681759_54221324) was identified as the second most frequent gain in the BRCA1-mutated population and has not yet been described in the context of BRCA1 mutation. We thus aimed to validate the expression of the Casein kinase 1 delta (CSNK1D) gene of Chr17 in TNBC and OC cell lines and to investigate the expression of genes of Chr19 in TNBC cell lines and tissues as well as in OC cell lines. Expression level of the genes of the 17q25.3, 19q13.32,13.33 and 13.41 chromosomal regions was analyzed using RT-PCR in BRCA1 deficient TNBC and OC cell lines, as well as in 10 BRCA1-mutated TNBC tissues versus 10 wild type carriers. Our results revealed a significant upregulation of CSNK1D gene expression in BRCA1 deficient TNBC and OC cell lines when compared to control ones, and a significant aberration in the expression of the other six genes of Chr19 was observed. Interestingly, upregulation of kallikrein-related peptidase 6 (KLK6) was detected among the BRCA1 deficient TNBC (cell lines and tissues) and OC cell lines. In conclusion, our results suggested that CSNK1D and KLK6 expression levels could be very promising in the search for biomarkers for BRCA1 deficient TNBC and OC.