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

Cancer. 1999 Mar 15;85(6):1389-94.

Abstract

Background: Insulin-like growth factor-2 (IGF2) and H19 are reciprocally imprinted genes on chromosome 11; IGF2 is expressed paternally and H19 is expressed maternally. Loss of imprinting (LOI) at both H19 and IGF2 has been reported 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 chain reaction (PCR) and screened for heterozygosity at both IGF2 and H19 using either ApaI or RsaI, respectively. If heterozygous, polyadenylated RNA was isolated and reversed-transcribed into cDNA. cDNA then was amplified by PCR and the products were digested with restriction enzymes to evaluate GCT expression of IGF2 and H19.

Results: Eleven pediatric GCTs were fully informative for H19 and IGF2, including 5 ovarian GCTs, 2 testicular GCTs, and 4 extragonadal GCTs. Consistent 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 timing of carcinogenesis in germ cells at these sites.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Genomic Imprinting*
  • Germinoma / genetics*
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Muscle Proteins / analysis
  • Muscle Proteins / genetics*
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • RNA, Long Noncoding
  • RNA, Untranslated*
  • Testicular Neoplasms / chemistry
  • Testicular Neoplasms / genetics

Substances

  • H19 long non-coding RNA
  • Muscle Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated