Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinomas and underlying disease

Shin Takeda, Masashi Kondo, Takashi Kumada, Takashi Koshikawa, Ryuzo Ueda, Masayuki Nishio, Hirotaka Osada, Hiroko Suzuki, Masaaki Nagatake, Osuke Washimi, Kenzo Takagi, Toshitada Takahashi, Akimasa Nakao, Takashi Takahashi

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

It has been well documented that the liver is an exceptional organ in which the monoallelic expression of insulin-like growth factor 2 (IGF2) due to genomic imprinting is relaxed during the postnatal period, resulting in biallelic expression thereafter. In the present study, changes in the status of genomic imprinting were examined in 15 hepatocellular carcinomas (HCCs) as well as in 29 liver biopsies of chronic hepatitis or liver cirrhosis without clinical evidence of HCC, following screening for heterozygotes with an ApaI polymorphism in IGF2 in 34 HCCs and 80 such non-HCC cases. Extreme allelic-expression imbalance, leading to restoration of monoallelic IGF2 expression, was observed in 15 (100%) of 15 informative HCCs for the polymorphism with this monoallelic IGF2 expression appearing to be non-random from the paternal allele. Interestingly, the same allelic-expression imbalance was also present in a significant fraction of noncancerous liver specimens of patients with underlying disease known to be associated with HCC development. In contrast, the status of genomic imprinting of H19, another gene closely mapped at 11p15 under opposite imprinting, was strictly maintained in seven (100%) of seven cases informative for an RsaI polymorphism of H19. Together with the previous reports on altered genomic imprinting of IGF2 and H19 in embryonal lesions such as Wilms tumors as well as in lung cancers, the results suggest that perturbations of imprinting status occur as locus and tumor-type specific events in the development of human cancers.

Original languageEnglish
Pages (from-to)1589-1592
Number of pages4
JournalOncogene
Volume12
Issue number7
Publication statusPublished - 13-05-1996
Externally publishedYes

Fingerprint

Allelic Imbalance
Genomic Imprinting
Somatomedins
Hepatocellular Carcinoma
Genes
Liver
Wilms Tumor
Human Development
Chronic Hepatitis
Heterozygote
Liver Cirrhosis
Lung Neoplasms
Neoplasms
Alleles
Carcinoma
Biopsy

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Takeda, S., Kondo, M., Kumada, T., Koshikawa, T., Ueda, R., Nishio, M., ... Takahashi, T. (1996). Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinomas and underlying disease. Oncogene, 12(7), 1589-1592.
Takeda, Shin ; Kondo, Masashi ; Kumada, Takashi ; Koshikawa, Takashi ; Ueda, Ryuzo ; Nishio, Masayuki ; Osada, Hirotaka ; Suzuki, Hiroko ; Nagatake, Masaaki ; Washimi, Osuke ; Takagi, Kenzo ; Takahashi, Toshitada ; Nakao, Akimasa ; Takahashi, Takashi. / Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinomas and underlying disease. In: Oncogene. 1996 ; Vol. 12, No. 7. pp. 1589-1592.
@article{1583ca9096dd4b578d111e80ecae5894,
title = "Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinomas and underlying disease",
abstract = "It has been well documented that the liver is an exceptional organ in which the monoallelic expression of insulin-like growth factor 2 (IGF2) due to genomic imprinting is relaxed during the postnatal period, resulting in biallelic expression thereafter. In the present study, changes in the status of genomic imprinting were examined in 15 hepatocellular carcinomas (HCCs) as well as in 29 liver biopsies of chronic hepatitis or liver cirrhosis without clinical evidence of HCC, following screening for heterozygotes with an ApaI polymorphism in IGF2 in 34 HCCs and 80 such non-HCC cases. Extreme allelic-expression imbalance, leading to restoration of monoallelic IGF2 expression, was observed in 15 (100{\%}) of 15 informative HCCs for the polymorphism with this monoallelic IGF2 expression appearing to be non-random from the paternal allele. Interestingly, the same allelic-expression imbalance was also present in a significant fraction of noncancerous liver specimens of patients with underlying disease known to be associated with HCC development. In contrast, the status of genomic imprinting of H19, another gene closely mapped at 11p15 under opposite imprinting, was strictly maintained in seven (100{\%}) of seven cases informative for an RsaI polymorphism of H19. Together with the previous reports on altered genomic imprinting of IGF2 and H19 in embryonal lesions such as Wilms tumors as well as in lung cancers, the results suggest that perturbations of imprinting status occur as locus and tumor-type specific events in the development of human cancers.",
author = "Shin Takeda and Masashi Kondo and Takashi Kumada and Takashi Koshikawa and Ryuzo Ueda and Masayuki Nishio and Hirotaka Osada and Hiroko Suzuki and Masaaki Nagatake and Osuke Washimi and Kenzo Takagi and Toshitada Takahashi and Akimasa Nakao and Takashi Takahashi",
year = "1996",
month = "5",
day = "13",
language = "English",
volume = "12",
pages = "1589--1592",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "7",

}

Takeda, S, Kondo, M, Kumada, T, Koshikawa, T, Ueda, R, Nishio, M, Osada, H, Suzuki, H, Nagatake, M, Washimi, O, Takagi, K, Takahashi, T, Nakao, A & Takahashi, T 1996, 'Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinomas and underlying disease', Oncogene, vol. 12, no. 7, pp. 1589-1592.

Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinomas and underlying disease. / Takeda, Shin; Kondo, Masashi; Kumada, Takashi; Koshikawa, Takashi; Ueda, Ryuzo; Nishio, Masayuki; Osada, Hirotaka; Suzuki, Hiroko; Nagatake, Masaaki; Washimi, Osuke; Takagi, Kenzo; Takahashi, Toshitada; Nakao, Akimasa; Takahashi, Takashi.

In: Oncogene, Vol. 12, No. 7, 13.05.1996, p. 1589-1592.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinomas and underlying disease

AU - Takeda, Shin

AU - Kondo, Masashi

AU - Kumada, Takashi

AU - Koshikawa, Takashi

AU - Ueda, Ryuzo

AU - Nishio, Masayuki

AU - Osada, Hirotaka

AU - Suzuki, Hiroko

AU - Nagatake, Masaaki

AU - Washimi, Osuke

AU - Takagi, Kenzo

AU - Takahashi, Toshitada

AU - Nakao, Akimasa

AU - Takahashi, Takashi

PY - 1996/5/13

Y1 - 1996/5/13

N2 - It has been well documented that the liver is an exceptional organ in which the monoallelic expression of insulin-like growth factor 2 (IGF2) due to genomic imprinting is relaxed during the postnatal period, resulting in biallelic expression thereafter. In the present study, changes in the status of genomic imprinting were examined in 15 hepatocellular carcinomas (HCCs) as well as in 29 liver biopsies of chronic hepatitis or liver cirrhosis without clinical evidence of HCC, following screening for heterozygotes with an ApaI polymorphism in IGF2 in 34 HCCs and 80 such non-HCC cases. Extreme allelic-expression imbalance, leading to restoration of monoallelic IGF2 expression, was observed in 15 (100%) of 15 informative HCCs for the polymorphism with this monoallelic IGF2 expression appearing to be non-random from the paternal allele. Interestingly, the same allelic-expression imbalance was also present in a significant fraction of noncancerous liver specimens of patients with underlying disease known to be associated with HCC development. In contrast, the status of genomic imprinting of H19, another gene closely mapped at 11p15 under opposite imprinting, was strictly maintained in seven (100%) of seven cases informative for an RsaI polymorphism of H19. Together with the previous reports on altered genomic imprinting of IGF2 and H19 in embryonal lesions such as Wilms tumors as well as in lung cancers, the results suggest that perturbations of imprinting status occur as locus and tumor-type specific events in the development of human cancers.

AB - It has been well documented that the liver is an exceptional organ in which the monoallelic expression of insulin-like growth factor 2 (IGF2) due to genomic imprinting is relaxed during the postnatal period, resulting in biallelic expression thereafter. In the present study, changes in the status of genomic imprinting were examined in 15 hepatocellular carcinomas (HCCs) as well as in 29 liver biopsies of chronic hepatitis or liver cirrhosis without clinical evidence of HCC, following screening for heterozygotes with an ApaI polymorphism in IGF2 in 34 HCCs and 80 such non-HCC cases. Extreme allelic-expression imbalance, leading to restoration of monoallelic IGF2 expression, was observed in 15 (100%) of 15 informative HCCs for the polymorphism with this monoallelic IGF2 expression appearing to be non-random from the paternal allele. Interestingly, the same allelic-expression imbalance was also present in a significant fraction of noncancerous liver specimens of patients with underlying disease known to be associated with HCC development. In contrast, the status of genomic imprinting of H19, another gene closely mapped at 11p15 under opposite imprinting, was strictly maintained in seven (100%) of seven cases informative for an RsaI polymorphism of H19. Together with the previous reports on altered genomic imprinting of IGF2 and H19 in embryonal lesions such as Wilms tumors as well as in lung cancers, the results suggest that perturbations of imprinting status occur as locus and tumor-type specific events in the development of human cancers.

UR - http://www.scopus.com/inward/record.url?scp=9244257359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9244257359&partnerID=8YFLogxK

M3 - Article

VL - 12

SP - 1589

EP - 1592

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 7

ER -