Genomic imprinting of H19 and insulin-like growth factor-2 in pediatric germ cell tumors

BACKGROUND. Insulin-like growth factor-2 (IGF2) and H19 are reciprocally im printed genes on chromosome 11; IGF2 is expressed paternally and H19 is exp ressed maternally. Loss of imprinting (LOI) at both H19 and IGF2 has been r eported in seven fully informative adult testicular germ cell tumors (GCTs) and may contribute to germ cell carcinogenesis. METHODS. Genomic DNA from 61 pediatric GCTs was amplified by polymerase cha in reaction (PCR) and screened for heterozygosity at both IGF2 and H19 usin g either ApaI or RsaI, respectively. If heterozygous, polyadenylated RNA wa s isolated and reversed-transcribed into cDNA. cDNA then was amplified by P CR and the products were digested with restriction enzymes to evaluate CCT expression of IGF2 and H19. RESULTS. Eleven pediatric GCTs were fully informative for H19 and IGF2, inc luding 5 ovarian GCTs, 2 testicular GCTs, and 4 extragonadal GCTs. Consiste nt with prior studies, both testicular GCTs showed LOI at both H19 and IGF2 . In contrast, three of the five ovarian GCTs had LOI at both IGF2 and H19; one had LOI at IGF2 only, and one retained imprinting; at both loci. Only one of the four extragonadal GCTs had LOI at IGF2 whereas three of the four had LOI at H19. CONCLUSIONS. These data suggest that LOI at H19 and IGF2 also may be common in pediatric testicular GCTs. However, ovarian and extragonadal pediatric GCTs showed variable patterns of LOI that may indicate differences in the t iming of carcinogenesis in germ cells at these sites. Cancer 1999;85:1389-9 4. (C) 1999 American Cancer Society.