ARID1A , NOTCH and WNT Signature in Gynaecological Tumours.

Ovarian cancer (OC) is among the deadliest gynaecologic malignancies in the world. The majority of OC patients are diagnosed at an advanced stage, with high-grade serous OC (HGSOC). The lack of specific symptoms and suitable screening strategies lead to short progression-free survival times in HGSOC patients. The chromatin-remodelling, WNT and NOTCH pathways are some of the most dysregulated in OC; thus their gene mutations and expression profile could serve as diagnostic or prognostic OC biomarkers. Our pilot study investigated mRNA expression of the SWI/SNF chromatin-remodelling complex gene , NOTCH receptors, WNT pathway genes and mRNA expression in two OC cell cultures as well as 51 gynaecologic tumour tissues. A four-gene panel consisting of , , and was used to investigate mutations in gynaecologic tumour tissue. All seven analysed genes were found to be significantly downregulated in OC when compared with non-malignant gynaecologic tumour tissues. was also downregulated in SKOV3 cells when compared to A2780. Fifteen mutations were found in 25.5% (13/51) of the tissue samples. predicted mutations were the most prevalent with alterations detected in 19% (6/32) HGSOC and 67% (6/9) of other OC cases. Thus, and NOTCH/WNT-pathway-related changes could be useful diagnostic biomarkers in OC.