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

研究成果: Article

76 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)5007-5011
ページ数5
ジャーナルCancer Research
55
発行部数21
出版物ステータスPublished - 01-11-1995
外部発表Yes

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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

これを引用

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. :: Cancer Research. 1995 ; 巻 55, 番号 21. pp. 5007-5011.
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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.",
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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, 巻. 55, 番号 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.

:: Cancer Research, 巻 55, 番号 21, 01.11.1995, p. 5007-5011.

研究成果: Article

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T1 - Biallelic Inactivation of the APC Gene in Hepatoblastoma

AU - Kurahashi, Hiroki

AU - Takami, Koji

AU - Nishisho, Isamu

AU - Kurahashi, Hiroki

AU - Tawa, Akio

AU - Okada, Shintaro

AU - Oue, Takaharu

AU - Kusafuka, Takeshi

AU - Okada, Akira

PY - 1995/11/1

Y1 - 1995/11/1

N2 - 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.

AB - 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.

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Kurahashi H, Takami K, Nishisho I, Kurahashi H, Tawa A, Okada S その他. Biallelic Inactivation of the APC Gene in Hepatoblastoma. Cancer Research. 1995 11 1;55(21):5007-5011.