Abstract 4851: MicroRNA expression in childhood germ cell tumors (GCT).

Abstract

Abstract Introduction: Childhood germ cell tumors (GCTs) are a rare, heterogeneous group of malignancies classified together due to a common origin in the primordial germ cell. Studies in adults and a mouse stem cell model suggest microRNA (miRNA) expression may be involved in GCT etiology. We evaluated whether miRNA expression differed in pediatric GCTs with respect to tumor histology as well as by patient age at diagnosis and sex. Methods: MiRNA expression was measured in 44 samples from 38 individuals (38 GCT and 6 normal adjacent) using the NCounter platform (NanoString Technologies, Seattle, WA) which precisely quantifies discrete counts up to 800 miRNAs by imaging color-coded molecular barcodes. We compared miRNA expression across the main histologic subtypes of GCT (8 yolk sac tumor (YST), 8 dysgerminoma, 8 immature teratoma, and 10 mature teratoma) using NanoStride software, which analyzes raw count data from NCounter to perform differential expression analysis by employing the appropriate negative binomial distributional assumption and Benjamini-Hochberg correction (BH) for multiple testing. Results: Assessing all samples together, three miRNA species were found to significantly differ across the five categories (four tumor histologies and normal samples) (hsa-miR-371-5p, BH q-value 0.006; hsa-miR-122, BH q-value 0.03; and hsa-miR-302d, BH q-value 0.03). YSTs showed substantially higher expression of both hsa-miR-302d and hsa-miR-122 compared to all other histologies, while dysgerminomas exhibited considerably higher levels of hsa-miR-371-5. Upon pairwise analysis, YSTs differed from dysgerminomas with respect to four miRNA species (hsa-miR-375, BH q-value 0.009; hsa-miR-122, BH q-value 0.01; hsa-miR-296-5p, BH q-value 0.04; hsa-miR-1247, BH q-value 0.04) and from mature teratomas with respect to three miRNAs (hsa-miR-302d BH q-value 0.005; hsa-miR-122 BH q-value 0.008; hsa-miR-302a, BH q-value 0.01). No differences were found with respect to patient age at diagnosis or sex. When grouping all tumor samples together and comparing them to normal samples, no differences were found. Discussion: These results indicate differential expression of miRNA species by tumor histology in GCT. These could be reflective of malignancy or simply cell type as the most persistent differences were across histologic subtype not between malignant and normal samples. While differences were not found between malignant and normal samples after correction, the most significantly different species from that analysis–the miRNA 371-73 and miRNA-302 cluster–have been previously identified as differential in adult GCTs. Further study is needed to identify the RNA targets of these miRNAs and to determine their functional significance in GCTs. If confirmed in larger studies, these results suggest that miRNAs may play a significant role in childhood GCT. Citation Format: Jessica R.B. Musselman, Julie A. Ross, Weihua Guan, Jenny N. Poynter. MicroRNA expression in childhood germ cell tumors (GCT). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4851. doi:10.1158/1538-7445.AM2013-4851