Biallelic Inactivation of the APC Gene in Hepatoblastoma

Hiroki Kurahashi, Koji Takami, Isamu Nishisho, Hiroki Kurahashi, Akio Tawa, Shintaro Okada, Takaharu Oue, Takeshi Kusafuka, Akira Okada

Research output: Contribution to journalArticle

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Abstract

Familial adenomatous polyposis (FAP) is an inherited disorder caused by germline mutation of the adenomatous polyposis coli (APC) gene. Increased risk of hepatoblastoma (HBL) in FAP kindreds has been reported. To determine whether inactivation of the APC gene plays a role in development of HBL, 13 sporadic infantile hepatic tumors were analyzed for genetic alterations in the APC gene. A PCR-mediated RNase protection analysis was performed to detect subtle genetic alterations in the mutation cluster region and in exons 3 and 4 of the APC gene. The results showed that a G to T transversion at the splice acceptor site of the intron 3-exon 4 junction had occurred in one HBL. Sequence analysis of normal tissue of the patient proved the mutation to be germinal. Southern blot analysis at the APC locus revealed that the tumor had lost the opposite allele and was isodisomic at this locus. UNA analysis indicated that the tumor contained only the small APC transcript, from which exon 4 was entirely absent Since abnormal splicing causes termination due to frame-shift, it was hypothesized that only the truncated APC protein was expressed in this tumor. These findings suggest that inactivation of the APC gene is closely related to tumorigenesis of HBLs in FAP patients.

Original languageEnglish
Pages (from-to)5007-5011
Number of pages5
JournalCancer Research
Volume55
Issue number21
Publication statusPublished - 01-11-1995
Externally publishedYes

Fingerprint

APC Genes
Hepatoblastoma
Adenomatous Polyposis Coli
Exons
Neoplasms
Adenomatous Polyposis Coli Protein
RNA Splice Sites
Mutation
Germ-Line Mutation
Ribonucleases
Southern Blotting
Introns
Sequence Analysis
Carcinogenesis
Alleles
Polymerase Chain Reaction
Liver

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kurahashi, H., Takami, K., Nishisho, I., Kurahashi, H., Tawa, A., Okada, S., ... Okada, A. (1995). Biallelic Inactivation of the APC Gene in Hepatoblastoma. Cancer Research, 55(21), 5007-5011.
Kurahashi, Hiroki ; Takami, Koji ; Nishisho, Isamu ; Kurahashi, Hiroki ; Tawa, Akio ; Okada, Shintaro ; Oue, Takaharu ; Kusafuka, Takeshi ; Okada, Akira. / Biallelic Inactivation of the APC Gene in Hepatoblastoma. In: Cancer Research. 1995 ; Vol. 55, No. 21. pp. 5007-5011.
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Kurahashi, H, Takami, K, Nishisho, I, Kurahashi, H, Tawa, A, Okada, S, Oue, T, Kusafuka, T & Okada, A 1995, 'Biallelic Inactivation of the APC Gene in Hepatoblastoma', Cancer Research, vol. 55, no. 21, pp. 5007-5011.

Biallelic Inactivation of the APC Gene in Hepatoblastoma. / Kurahashi, Hiroki; Takami, Koji; Nishisho, Isamu; Kurahashi, Hiroki; Tawa, Akio; Okada, Shintaro; Oue, Takaharu; Kusafuka, Takeshi; Okada, Akira.

In: Cancer Research, Vol. 55, No. 21, 01.11.1995, p. 5007-5011.

Research output: Contribution to journalArticle

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Kurahashi H, Takami K, Nishisho I, Kurahashi H, Tawa A, Okada S et al. Biallelic Inactivation of the APC Gene in Hepatoblastoma. Cancer Research. 1995 Nov 1;55(21):5007-5011.