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 language | English (US) |
|---|---|
| Journal | Cancer Research |
| Volume | 59 |
| Issue number | 7 SUPPL. |
| State | Published - Apr 1 1999 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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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 journal › Article
}
TY - JOUR
T1 - Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer
T2 - An introduction
AU - Feinberg, Andrew P
PY - 1999/4/1
Y1 - 1999/4/1
N2 - 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.
AB - 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.
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M3 - Article
VL - 59
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 7 SUPPL.
ER -