Pediatric pineal germinomas: Epigenetic and genomic approach

•The pineal germinoma can share chromosomal alterations with gonadal tumors.•Amplification in 1q24.2, 1q31.3 and 1q21.3 are the most important in pineal germinoma.•The deletions in 11q11 is the most important in germ cell tumors.•The genes PPAPDC1B and NPC2 play an important role in the tumorigenesis.

ObjectiveWe identify and correlate chromosomal alterations, methylation patterns and gene expression in pediatric pineal germinomas.MethodsCGH microarray, methylation and gene expression were performed through the Agilent platform. The results were analyzed with MatLab software, MapViewer, DAVID, GeneCards and Hippie.ResultsAmplifications were found in 1q24.2, 1q31.3, 2p11.2, 3p22.2, 7p13, 7p15.2, 8p22, 12p13.2, 14q24.3 y 22q12; and deletions were found in 1q21.2, 9p24.1, 10q11.22, 11q11, 15q11.2 and 17q21.31. In the methylation analysis, we observed 10,428 CpG Islands with a modified methylation status that may affect 11,726 genes. We identified 1260 overexpressed genes and 470 underexpressed genes. The genes RUNDC3A, CDC247, CDCA7L, ASAH1, TRA2A, LPL and NPC2 were altered among the three levels.ConclusionsWe identified the 1q24.2 and 1q31.3 amplified regions and the 1q21.3 and 11q11 deleted regions as the most important aims. The genes NPC2 and ASAH1 may play an important role in the development, progression and tumor maintenance. The ASAH1 gene is an ideal candidate to identify drug responses. These genomic and epigenetic studies may help to characterize the formation of pineal germ cell tumors to determine prognostic markers and also to identify shared characteristics in gonadal and extragonadal tumors.