CCND1 and PTEN gene copy number variations as markers of vulvar cancer progression.

Abstract

e17531 Background: More than 90% of malignant vulvar tumors and almost 5% of all gynecological cancers are squamous cell carcinoma. 1/3 of patients with vulvar cancer relapse after initial treatment, and the 2-year overall survival is less than 15%. Development of more effective treatments requires understanding of the molecular pathogenesis of vulvar cancer. The aim of this study was the screening of potential prognostic tumor markers in vulvar cancer based on relative copy number analysis (CNV) of MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, AEPX1, NFKBIA, MTAP, BIRC2, SYNE1, KMT2C genes. Methods: The study was performed on 300 patients aged 29-80 years diagnosed with vulvar squamous cell carcinoma with lymph nodes metastases (n = 150) and without metastases (n = 150). The material for the study was DNA from FFPE-blocks of tumor and non-tumor vulvar tissues. The RT-qPCR method was used to evaluate the relative copy number of MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, AEPX1, NFKBIA, MTAP, BIRC2, SYNE1, KMT2C, GAPDH and B2M genes (the last two were reference genes). Differences were assessed using the Mann-Whitney test (Bonferroni correction was used). Results: All genes showed a change in the dose in vulva tumor cells relative to normal ones: amplifications for the MYC, MCL1, AEPX1, NFKBIA, CCND1, PIK3CA, TP53, MDM2, BIRC2, SYNE1, KMT2C genes, respectively, in 46%, 36%, 28%, 40%, 56%, 43%, 62%, 39%, 57%, 35%, 44% of cases, and a decrease in copy number for PTEN, MTAP, CDKN2A genes, respectively, in 34%, 28%, 35% of cases. At the same time, a statistically significant increase in the CNV of the CCND1 gene (p < 0.05) by 1.7 times and a decrease in the PTEN gene (p < 0.05) by 1.9 times were observed in the group of vulvar squamous cell carcinoma patients with lymph nodes metastases. No statistically significant change in the CNV of other genes was found. Conclusions: Thus, the identified aberrant copy numbers of CCND1 and PTEN genes can serve as prognostic markers for vulvar cancer patients.