DNA copy amplification and overexpression of SLC12A7 in adrenocortical carcinoma DISCUSSION

Background. Overexpression of Solute carrier family 12 member 7 (SLC12A7) promotes tumor aggressiveness in various cancers. Previous studies have identified the 5p15.33 region, containing the SLC12A7 locus, as being amplified frequently in adrenocortical carcinoma (ACC). Copy number amplifications (CNAs) may alter gene expression levels and occur frequently in ACC; however, SLC12A7 gene amplifications or expression levels have not been studied in ACC. Methods. Fifty-five cases of clinically well-characterized ACCs were recruited for this study. Whole-exome sequencing was used to predict CNAs in 19 samples. CNA analysis was performed on an expanded cohort of 26 samples with the use of TaqMan Copy Number Assays. SLC12A7 mRNA expression was analyzed in 32 samples with real-time quantitative polymerase chain reaction and protein expression was assessed by immunohistochemistry. SLC12A7 CNAs and expression patterns were evaluated for correlation with patient and tumor characteristics. Results. Whole-exome sequencing and TaqMan Copy Number Assays demonstrated SLC12A7 amplifications in 68.4% and 65.4% of ACCs tested, respectively. Furthermore, SLC12A7 copy gains were associated with increased gene expression (P < .05) and non-functional tumors (P < .05). SLC12A7 gene expression levels were increased in ACCs compared with normal adrenal tissue (P < .05). Conclusion. SLC12A7 gene amplification and overexpression occurs frequently in ACCs and may represent a novel molecular event associated with ACC.