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Genomic imprinting of H19 and insulin‐like growth factor‐2 in pediatric germ cell tumors
Author(s) -
Ross Julie A.,
Schmidt Peter T.,
Perentesis John P.,
Davies Stella M.
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990315)85:6<1389::aid-cncr24>3.0.co;2-v
Subject(s) - genomic imprinting , imprinting (psychology) , medicine , beckwith–wiedemann syndrome , insulin like growth factor , insulin like growth factor 2 , cancer research , germ cell , growth factor , genetics , biology , gene , dna methylation , gene expression , receptor
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 Apa I or Rsa I, 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. Cancer 1999;85:1389–94. © 1999 American Cancer Society.