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Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma
- Source :
- Oncogene. 23:8292-8300
- Publication Year :
- 2004
- Publisher :
- Springer Science and Business Media LLC, 2004.
-
Abstract
- APAF-1 gene, located at chromosome locus 12q23, is a key factor in the mitochondrial apoptotic pathway downstream 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.
- Subjects :
- Cancer Research
Tumor suppressor gene
Biology
medicine.disease_cause
Metastasis
Genetics
medicine
Humans
RNA, Messenger
Promoter Regions, Genetic
Molecular Biology
Alleles
Chromosomes, Human, Pair 12
Liver Neoplasms
Chromosome Mapping
Proteins
Microsatellite instability
DNA Methylation
medicine.disease
Primary tumor
digestive system diseases
Apoptotic Protease-Activating Factor 1
Tumor progression
Immunology
Allelic Imbalance
Disease Progression
Cancer research
Colorectal Neoplasms
Carcinogenesis
Haploinsufficiency
Microsatellite Repeats
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....f06bdf8c650e010e23e717a6051f5b09