Abstract A01: Genome-wide changes in expression of small RNAs in human testis cancer tissue

Abstract

Abstract Testicular germ cell tumor (TGCT) is the most common malignancy in young men in most western countries. The incidence is highest in Northern European populations, where the incidence rates have increased significantly over the past decades. Genetic predisposition and conditions during pregnancy play a central role in TGCT development, and the disease arises from primordial germ cells that develop into carcinoma in situ (CIS) lesions. These lesions may develop into cancer from puberty onwards. Like primordial germ cells, CIS cells retain a permissive chromatin structure, indicating the involvement of epigenetic components in TGCT. To assess the role of small RNAs in testicular carcinogenesis, we quantified small RNAs (19 to 35 bp) in 25 human cancer samples with differing TGCT histology and 12 normal testis samples using small RNA sequencing. piRNA expression levels were calculated for piRNA clusters built on the small RNA dataset generated from the 37 samples. Most piRNA clusters differ substantially in expression between TGCT samples and healthy controls, indicating a common mechanism for this genome-wide effect. In addition, a total of 101 miRNAs show differential expression between healthy tissue and TGCT samples (p<0.1 when adjusting for multiple testing with the Benjamini-Hochberg procedure). Twenty miRNAs have p<1×10-6, including miRNAs previously implicated in TGCT development and in cisplatin sensitivity. Furthermore, clustering demonstrates unique miRNA expression in different TGCT histological subtypes. These results indicate that small RNAs could be used as TGCT markers and potentially be a powerful tool in aiding diagnosis and identification of histological subtypes in TGCT patients, as well as in development of new therapeutic interventions. Citation Format: Trine Ballestad Rounge, Kari Furu, Rolf Inge Skotheim, Espen Enerly, Trine Berit Haugen, Tom Grotmol. Genome-wide changes in expression of small RNAs in human testis cancer tissue. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A01.