Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma

Naoyuki Umetani, Akihide Fujimoto, Hiroya Takeuchi, Masaru Shinozaki, Anton J. Bilchik, Dave S B Hoon

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

APAF-1 gene, located at chromosome locus 12q23, is a key factor in the mitochondrial apoptotic pathway down-stream of p53, and is a potential tumor suppressor gene. We hypothesized that APAF-1 gene dysfunction due to allelic imbalance (AI) contributes to the development and progression of colorectal carcinoma (CRC). AI at APAF-1 locus and microsatellite instability (MIN) in CRCs and adenomas were assessed by multiple microsatellite markers. The frequency of AI significantly increased with tumor progression; 0 of 33 (0%) adenomas, 14 of 49 (29%) primary CRCs, and 18 of 34 (53%) liver metastases had AI. A total of 12 metastases were matched with corresponding primary CRCs; in 11 of 12 (92%) pairs, the metastasis had same AI status as the corresponding primary tumor. APAF-1 mRNA transcription level was significantly decreased with AI in liver metastases (P=0.009). Promoter hypermethylation was found in three of 35 (9%) primary CRCs and one of 15 (7%) liver metastases by methylation-specific PCR but was not correlated with AI. MIN was observed in 11 of 49 (23%) primary CRCs and was a favorable prognostic factor. Our results suggest that APAF-1 gene haploinsufficiency caused by AI increases with tumor progression, and relates to hepatic metastasis.

Original languageEnglish
Pages (from-to)8292-8300
Number of pages9
JournalOncogene
Volume23
Issue number50
DOIs
Publication statusPublished - 2004 Oct 28
Externally publishedYes

Fingerprint

Allelic Imbalance
Colorectal Neoplasms
Neoplasm Metastasis
Microsatellite Instability
Liver
Adenoma
Genes
Haploinsufficiency
Neoplasms
Tumor Suppressor Genes
Microsatellite Repeats
Methylation
Chromosomes
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Allelic imbalance
  • APAF-1
  • Apoptosis
  • Chromosome 12q23
  • Colorectal carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Umetani, N., Fujimoto, A., Takeuchi, H., Shinozaki, M., Bilchik, A. J., & Hoon, D. S. B. (2004). Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma. Oncogene, 23(50), 8292-8300. https://doi.org/10.1038/sj.onc.1208022

Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma. / Umetani, Naoyuki; Fujimoto, Akihide; Takeuchi, Hiroya; Shinozaki, Masaru; Bilchik, Anton J.; Hoon, Dave S B.

In: Oncogene, Vol. 23, No. 50, 28.10.2004, p. 8292-8300.

Research output: Contribution to journalArticle

Umetani, N, Fujimoto, A, Takeuchi, H, Shinozaki, M, Bilchik, AJ & Hoon, DSB 2004, 'Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma', Oncogene, vol. 23, no. 50, pp. 8292-8300. https://doi.org/10.1038/sj.onc.1208022
Umetani N, Fujimoto A, Takeuchi H, Shinozaki M, Bilchik AJ, Hoon DSB. Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma. Oncogene. 2004 Oct 28;23(50):8292-8300. https://doi.org/10.1038/sj.onc.1208022
Umetani, Naoyuki ; Fujimoto, Akihide ; Takeuchi, Hiroya ; Shinozaki, Masaru ; Bilchik, Anton J. ; Hoon, Dave S B. / Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma. In: Oncogene. 2004 ; Vol. 23, No. 50. pp. 8292-8300.
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