Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer

An introduction

Research output: Contribution to journalArticle

Abstract

Our laboratory has found genomic imprinting of a large genomic domain of human 11p15.5, identifying six imprinted genes within this domain: (a) insulin-like growth factor II (IGF-II), an important autocrine growth factor in a wide variety of malignancies; (b) H19, an untranslated RNA that is a putative growth suppressor gene regulating IGF-II; (c) p57(KIP2), a cyclin- dependent kinase inhibitor that causes G1-S arrest; (d) K(v)LQT1, a voltage- gated potassium channel; (e) TSSC3, a gene that is homologous to mouse TDAG51, which is implicated in Fas-mediated apoptosis; and (f) TSSC5, a putative transmembrane protein-encoding gene. We hypothesize that 11p15 harbors a large domain of imprinted growth-regulatory genes that are important in cancer. Several lines of evidence support this hypothesis: (a) we have discovered a novel genetic alteration in cancer, loss of imprinting, which affects several of these genes, and is one of the most common genetic changes in human cancer; (b) we have found that the hereditary disorder Beckwith-Wiedemann syndrome, which predisposes to cancer and causes prenatal overgrowth, involves alterations in p57(KIP2), IGF-II, H19, and K(v)LQT1; (c) we have found both genetic (somatic mutation in Wilms' tumor) and epigenetic alterations (DNA methylation) in cancer; and (d) we can partially reverse abnormal imprinting using an inhibitor of DNA methylation. We propose a model of genomic imprinting as a dynamic developmental process involving a chromosomal domain. According to this model, cancer involves both genetic and epigenetic mechanisms affecting this imprinted domain and the genes within it.

Original languageEnglish (US)
JournalCancer Research
Volume59
Issue number7 SUPPL.
StatePublished - Apr 1 1999

Fingerprint

Genomic Imprinting
Insulin-Like Growth Factor II
Neoplasms
DNA Methylation
Epigenomics
Genes
Beckwith-Wiedemann Syndrome
Voltage-Gated Potassium Channels
Untranslated RNA
Wilms Tumor
Cyclin-Dependent Kinases
Regulator Genes
Tumor Suppressor Genes
Intercellular Signaling Peptides and Proteins
Apoptosis
Mutation
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer : An introduction. / Feinberg, Andrew P.

In: Cancer Research, Vol. 59, No. 7 SUPPL., 01.04.1999.

Research output: Contribution to journalArticle

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