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

研究成果: Article査読

30 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)8292-8300
ページ数9
ジャーナルOncogene
23
50
DOI
出版ステータスPublished - 2004 10 28

ASJC Scopus subject areas

  • 分子生物学
  • 遺伝学
  • 癌研究

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