Epigenetic differences between Wilms' tumours in white and east-Asian children
Variations in the international incidence of Wilms' tumour might be due to genetic factors. The maternal insulin-like growth factor 2 gene ( IGF2) is imprinted in normal tissues, whereas in some Wilms' tumours and other tumour types the imprint is lost, leading to biallelic transcription o...
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Published in | The Lancet (British edition) Vol. 363; no. 9407; pp. 446 - 451 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Elsevier Ltd
07.02.2004
Lancet Elsevier Limited |
Subjects | |
Online Access | Get full text |
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Summary: | Variations in the international incidence of Wilms' tumour might be due to genetic factors. The maternal insulin-like growth factor 2 gene (
IGF2) is imprinted in normal tissues, whereas in some Wilms' tumours and other tumour types the imprint is lost, leading to biallelic transcription of
IGF2. We investigated whether the difference in incidence of Wilms' tumour between children of east-Asian descent and white children is due to variations in proportion of tumours with loss of
IGF2 imprinting (
IGF2 LOI).
We assessed
IGF2 LOI by use of an
ApaI polymorphism in
IGF2 exon 9 or quantitative PCR measuring DNA methylation of the
H19 and
KvDMR1 alleles. The frequencies of perilobar nephrogenic rests associated with Wilms' tumour were assessed histologically in Japanese children and children of white and east-Asian descent.
IGF2 LOI was present in Wilms' tumours from predominantly white children from New Zealand (13 of 41tumours) but absent in tumours from Japanese children (0 of 21 tumours; difference in proportions 0·32, 95% CI 0·07–0·52). Frequency of perilobar nephrogenic rests accompanying tumours from white American children (1192 of 5002, 24%) was significantly higher than in Japanese (one of 56, 1%, difference in proportions 0·22, 95% CI 0·14–0·25) and east-Asian American children (seven of 92, 8%, 0·16, 0·09–0·21).
Wilms' tumours in the east-Asian population rarely arise from the
IGF2 LOI mechanism frequently noted in white patients. Our findings that
IGF2 LOI and perilobar nephrogenic rests associated with this mechanism arise at low frequency in Japanese and east-Asian American children lend support to this conclusion. Variation in frequency of this epigenetic mechanism provides one explanation for the difference in incidence of Wilms' tumour between populations. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0140-6736 1474-547X |
DOI: | 10.1016/S0140-6736(04)15491-3 |