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

• Published in: Cancer research (Chicago, Ill.) Vol. 57; no. 20; pp. 4469 - 4473
• Main Authors: CUI, H, HEDBORG, F, HE, L, NORDENSKJÖLD, A, SANDSTEDT, B, PFEIFER-OHLSSON, S, OHLSSON, R
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.10.1997
• Subjects: Alleles; Animals; Biological and medical sciences; Chromosomes, Human, Pair 11; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Genomic Imprinting; Genotype; Humans; In Situ Hybridization; Insulin-Like Growth Factor II - biosynthesis; Insulin-Like Growth Factor II - genetics; Kidney - pathology; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Kidneys; Loss of Heterozygosity; Male; Medical sciences; Medicin och hälsovetenskap; Mice; Models, Biological; Muscle Proteins - genetics; Nephrology. Urinary tract diseases; Precancerous Conditions - genetics; Precancerous Conditions - pathology; RNA, Long Noncoding; RNA, Untranslated; Tumors of the urinary system; Wilms Tumor - genetics; Wilms Tumor - pathology; Kidney disease; Human; Urinary system disease; Genotype; Malignant tumor; Gene expression; Inactivation; Carcinogenesis; Insulin like growth factor 2; Genomic imprinting; Wilms tumor; Genetics; Tumor suppressor gene
• ISSN: 0008-5472; 1538-7445

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.