Abstract
Objective: KAI1 (CD82) is a metastasis suppressor gene known to be down-regulated in carcinomas of breast, prostate and many other organs. The mechanism of KAI1 down-regulation is complex and not well understood. Here, we investigate the role of 8 SNPs (not previously studied) in KAI1 gene that could influence its expression in tumor tissue samples of breast cancer patients from the Eastern province of Saudi Arabia. Methods:Single nucleotide polymorphisms (SNPs) in KAI1 gene were selected from the NCBI website (dbSNP) and were then filtered for those SNPs causing stop codon mutations (rs139889503 and rs150533529) or nonsynonymous mutation in the 5’-UTR (rs11541048, rs77359459, rs115500759, rs182579675, rs200238062, and rs372733853). SNPs genotyping was performed using TaqMan SNP Genotyping Assay and the results were correlated with KAI1 protein expression profile by immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) samples of breast cancer and control none-neoplastic tissues. Results: KAI1 expression by IHC was observed in all none-neoplastic breast tissue samples and only in 35% out of the 59 breast cancer tissue samples. None of the samples was homozygous for the stop codon allele A in the SNP rs139889503 or allele T in the SNP rs150533529. The SNPs in the 5-UTR, rs11541048, rs115500759, and rs182579675, were only present in the homozygous state for the G and C alleles respectively in both cancer and control samples. The other SNPs in the 5’-UTR (rs77359459, rs200238062, and rs372733853) had no significant difference in the allele distribution between KAI1 expressing or none-expressing tissue samples. Conclusion:Our findings showed no significant effect of the studied SNPs on down-regulation of KAI1 expression.
Highlights
Breast cancer is a common cancer in the Eastern Province of Saudi Arabia with a high mortality rate which is mostly associated with its dissemination
We investigate the role of 8 Single nucleotide polymorphisms (SNPs) in KAI1 gene that could influence its expression in tumor tissue samples of breast cancer patients from the Eastern province of Saudi Arabia
The remaining SNPs were further refined to SNPs which produce a stop codon or if they were nonsynonymous mutations and were in the 5’-untranslated region (Table 1)
Summary
Breast cancer is a common cancer in the Eastern Province of Saudi Arabia with a high mortality rate which is mostly associated with its dissemination. The mechanism behind down-regulation of KAI1 expression during cancer development is complex, mediated by transcription control, alternative splicing, and even post-translational remodeling (Tonoli and Barrett, 2005; Tsai et al, 2007; Lee et al, 2011). A few studies investigated gene mutation, loss of heterozygosity (LOH), or promoter hypermethylation as a cause of KAI1 down-regulation (Gao et al, 2003; Marreiros et al, 2003). One of the early studies revealed that neither mutation (on 10 prostatic cancer samples) nor allelic loss (on 34 prostatic cancer samples and 12 metastatic lymph nodes) is the cause of KAI1 gene down-regulation (Dong et al, 1995). A later report showed that loss of KAI1 expression is not related to mutation, LOH, epigenetic regulation of the promoter, or p53 mutation (Uzawa et al, 2002). A study on 52 ovarian carcinomas found a missense alteration at codon 241 (ATC to GTC), which causes valine to isoleucine substitution in the peptide sequence but it occurs in normal
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