SNRPN methylation patterns in germ cell tumors as a reflection of primordial germ cell development

Studies examining altered imprinted gene expression in cancer compare the o bserved expression pattern to the normal expression pattern for a given tis sue of origin, usually the somatic expression pattern for the imprinted gen e. Germ cell tumors (GCTs), however, require a developmental stage-dependen t comparison. To explore using methylation as an indicator of germ cell dev elopment, we determined the pattern of methylation at the 5' untranslated r egion of SNRPN in 89 GCTs from both children and adults. Fifty-one of 84 tu mors (60.7%) (12/30 (40%) of cultured pediatric GCTs, 23/36 (63.9%) of froz en adult GCTs, and 16/23 (69.5%) of frozen pediatric GCTs, with five sample s having results from both cultured and uncultured material) demonstrated a nonsomatic methylation pattern after dual digestion with Xbal, Notl, and S outhern blot analysis. In contrast, only 2 of 18 (11%) control samples (16 non-GCTs and 2 normal ovaries) exhibited a nonsomatic pattern. In both case s, the result was shown to be due to copy number differences between matern al and paternal homologs, unlike the GCTs in which there was no evidence of an uneven homolog number. A comparison of the data for only the gonadal GC Ts and the control data showed a highly significant difference in the propo rtion of tumors with methylation alterations at this locus (P=0.0000539). S ince there is no published evidence of the involvement of SNRPN methylation changes in the development of malignancy, the data suggest that the methyl ation pattern of SNRPN in GCTs reflects that of the primordial germ cell gi ving rise to the tumor. (C) 2001 Wiley-Liss, Inc.