Inactivation of H19, an imprinted and putative tumor repressor gene, is a preneoplastic event during Wilms' tumorigenesis

Genetic evidence shows that the parent of origin-dependent expression patterns of the Igf2 and H19 genes is coordinated in mouse, such that H19 controls the activity of Igf2 in cis. Equally compelling evidence for a similar situation in humans is absent, although the frequently observed activation of the maternal IGF2 allele (ie., loss of imprinting) in Wilms' tumors has been attributed to the silencing of the maternal H19 locus. We show here that loss of H19 activity is generally a preneoplastic event, which may be linked with an overgrowth lesion that has been proposed to be permissive for tumor formation. Although our results document one instance in which a postneoplastic loss of H19 activity correlates with loss of IGF2 imprinting at the cellular level, it appears that inactivation of H19 is more generally independent of loss of imprinting of IGF2, at least in our specimens. Our results imply that inactivation of H19 correlates with blastema overgrowth and can be independent of a regulatory role with respect to IGF2 imprinting status in cis.

Hedborg, FUppsala universitet,Institutionen för kvinnors och barns hälsa,Zoologisk utvecklingsbiologi,Barnonkologisk forskning/Lönnerholm (författare)
He, L (författare)
Nordenskjold, A (författare)
Pfeifer, SUppsala universitet,Institutionen för kvinnors och barns hälsa,Zoologisk utvecklingsbiologi,Barnonkologisk forskning/Lönnerholm (författare)
Ohlsson, RKarolinska Institutet,Uppsala universitet,Zoologisk utvecklingsbiologi(Swepub:uu)rolfohls (författare)
Sandstedt, BKarolinska Institutet (författare)
PfeiferOhlsson, S (författare)
Uppsala universitetInstitutionen för kvinnors och barns hälsa (creator_code:org_t)

Av författaren/redakt...: Cui, H; Hedborg, F; He, L; Nordenskjold, A; Pfeifer, S; Ohlsson, R; visa fler...; Sandstedt, B; PfeiferOhlsson, ...; visa färre...

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