Related Experiment Videos
Absence of secretory phospholipase A2 gene alterations in human colorectal cancer
G J Riggins1, S Markowitz, J K Wilson
1Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Abstract:
A potent modifying locus of intestinal tumorigenesis in the mouse was recently identified as secretory phospholipase A2 (sPLA2). The human homologue of sPLA2 maps to chromosome 1p35, a region frequently lost in human tumors. To evaluate the possibility that sPLA2 was a tumor suppressor gene that was the target of the 1p loss events, we identified polymorphisms within the human sPLA2 gene. Using these polymorphisms, 31% of 16 colorectal carcinomas were found to lose a sPLA2 allele. However, sequence analysis of the complete coding region of sPLA2 revealed no somatic mutations in the remaining allele of those tumors with allelic loss, nor in 18 additional colorectal cancers. Thus, sPLA2 is within the chromosomal region often lost during colorectal tumorigenesis, but mutations of this gene do not appear to play a major role in colorectal cancer development, and sPLA2 is unlikely to be the 1p35 tumor suppressor.
Insights
Secretory phospholipase A2 (sPLA2) is located in a region of chromosome 1p35 often lost in colorectal cancers. However, this study found no evidence that sPLA2 mutations drive colorectal cancer development.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- A mouse intestinal tumorigenesis locus, secretory phospholipase A2 (sPLA2), has a human homologue on chromosome 1p35.
- Chromosome 1p35 is frequently lost in human tumors, suggesting sPLA2 could be a tumor suppressor gene targeted by these losses.
Purpose of the Study:
- To investigate if secretory phospholipase A2 (sPLA2) functions as a tumor suppressor gene in colorectal cancer.
- To determine if mutations in the sPLA2 gene are associated with allelic loss at chromosome 1p35 in colorectal carcinomas.
Main Methods:
- Identification of polymorphisms within the human sPLA2 gene.
- Analysis of sPLA2 allele loss in 16 colorectal carcinomas using identified polymorphisms.
- Sequence analysis of the complete coding region of sPLA2 in tumors with allelic loss and 18 additional colorectal cancers.
Main Results:
- Allelic loss of sPLA2 was observed in 31% of the 16 colorectal carcinomas analyzed.
- No somatic mutations were detected in the remaining sPLA2 allele in tumors exhibiting allelic loss.
- No mutations were found in the sPLA2 gene in an additional 18 colorectal cancer cases.
Conclusions:
- Secretory phospholipase A2 (sPLA2) is located within a chromosomal region (1p35) frequently affected by loss of heterozygosity in colorectal cancer.
- Mutations in the sPLA2 gene do not appear to be a significant factor in the development of colorectal cancer.
- sPLA2 is unlikely to be the tumor suppressor gene responsible for the observed 1p35 loss events in colorectal tumorigenesis.