Correlation between the abnormalities of p53 and Rabphillin-3A-Like genes in colorectal adenocarcinoma Free

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Purpose: The human ortholog of Rabphillin-3A-Like gene (RPH3AL), located at 17p13.3, which is distal to p53 gene locus (17p13.1). High loss of heterozygosity (LOH) frequency has been reported previously in both regions in patients with various malignancies. The current study assessed whether the abnormalities of these two genes are associated with each other in colorectal adenocarcinomas (CRCs).

Methods: Fifty-one invasive CRCs (27 node positive and 24 node negative) were selected for this study. Frozen tissues of all these CRCs and their matching controls were evaluated for the mutational status of p53 and RPH3AL genes following RT-PCR and direct sequencing of the cDNA using gene specific primer sets. LOH status of these two loci was assessed using ABI 3100 genetic analyzer with 4 polymorphic markers which are close to the RPH3AL locus (D17S1866, D17S926, D17S849 and D17S643) and 2 markers of the p53 locus (TP53.PCR15 and TP53.PCR18).

Result: Mutational analysis detected 18 (35%) missense point mutations in p53 gene and 3 missense point mutations in the RPH3AL gene. Three cases which exhibited mutations in RPH3AL gene also had mutations in p53. The LOH analysis demonstrated that 25 (of 41 informative, 61%) cases were positive for LOH at 17p13.3 locus, and 18 (72%) of them were node positive at the time of diagnosis. Twenty-one cases (of 35 informative, 60%) exhibited LOH at 17p13.1, and 15 (71%) of them were node positive. Seventeen cases were found with LOH in both loci and 12 of these cases (71%) were node positive.

Conclusion: These findings suggest that there is a strong correlation between p53 and RPH3AL genes and both of them are involved in the progression colorectal adenocarcinoma. This work is supported partially by funds from the Departmentof Pathology, University of Alabama at Birmingham and by a grantfrom the National Institute of Health/National Cancer Institute(RO1-CA98932-01).