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 observed expression pattern to the normal expression pattern for a given tissue of origin, usually the somatic expression pattern for the imprinted gene. Germ cell tumors (GCTs), however, require a developmental stage-dependent comparison. To explore using methylation as an indicator of germ cell development, we determined the pattern of methylation at the 5' untranslated region of SNRPN in 89 GCTs from both children and adults. Fifty-one of 84 tumors (60.7%) (12/30 (40%) of cultured pediatric GCTs, 23/36 (63.9%) of frozen adult GCTs, and 16/23 (69.5%) of frozen pediatric GCTs, with five samples having results from both cultured and uncultured material) demonstrated a nonsomatic methylation pattern after dual digestion with XbaI, NotI, and Southern blot analysis. In contrast, only 2 of 18 (11%) control samples (16 non-GCTs and 2 normal ovaries) exhibited a nonsomatic pattern. In both cases, the result was shown to be due to copy number differences between maternal 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 GCTs and the control data showed a highly significant difference in the proportion of tumors with methylation alterations at this locus (P = 0.0000539). Since there is no published evidence of the involvement of SNRPN methylation changes in the development of malignancy, the data suggest that the methylation pattern of SNRPN in GCTs reflects that of the primordial germ cell giving rise to the tumor.
Bussey
K J
KJ
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Oregon, USA.
Lawce
H J
HJ
Himoe
E
E
Shu
X O
XO
Heerema
N A
NA
Perlman
E J
EJ
Olson
S B
SB
Magenis
R E
RE
D000293:Adolescent; D000328:Adult; D001324:Autoantigens / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics; D005854:Germ Cells / Q000254:growth & development* / Q000473:pathology; D018237:Germinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D014407:Tumor Cells, Cultured; D055517:snRNP Core Proteins
D001324:Autoantigens; D004273:DNA, Neoplasm; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D055517:snRNP Core Proteins