ABSTRACT
Several risk factors associated with colorectal cancer (CRC) have been identified including ß-catenin/CTNNB1 hotspot mutations. The levels of ß-catenin within a cell are regulated via phosphorylation of the N terminus of ß-catenin by GSK-3ß. Thus far three serines (S33, 37, 45) and one threonine (T41) are considered to be the substrates for GSK-3ß phosphorylation. In the present investigation an attempt was made to study the role of ß-catenin mutations in exon-3 in 60 colorectal cancer patients from Kingdom of Saudi Arabia (KSA). The hot spot mutation region of ß-catenin exon 3 was evaluated in matched tumor and normal tissues using PCR and direct sequencing. Sequencing of exon 3 of the CTNNB1 gene revealed an activating mutation (S33F) in one of the tumor samples as compared to the normal tissue from the same patient where there was no such mutation found. Immunohistochemical staining showed the accumulation of ß-catenin protein both in cytoplasm and in the nuclei of cancer cells as compared to normal tissue.
Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Mutation , beta Catenin/genetics , beta Catenin/metabolism , Colorectal Neoplasms/pathology , DNA Mutational Analysis , Female , Humans , Immunohistochemistry , Male , Middle Aged , Polymorphism, Single Nucleotide , Reverse Transcriptase Polymerase Chain Reaction , Saudi ArabiaABSTRACT
The non-classical class I human leukocyte antigen (HLA)-G molecule was found to be predominately expressed in the extravillous cytotrophoblasts at the fetal-maternal interface during pregnancy. This molecule is critically important for successful implantation during human pregnancy. The polymorphic insertion-deletion (indel) 14-base pair (bp) site localized at the 3' untranslated region was associated with HLA-G mRNA stability and isoform alternative splicing patterns, and thus may influence HLA-G function during pregnancy. We studied the association between the 14-bp indel polymorphism (rs16375) at the 3' untranslated region with recurrent spontaneous abortions in a Saudi population living in Riyadh. A group of 64 women with 2-11 successive abortions were included in this study. The control group included 62 women without reported abortions and at least 2 pregnancies, all visiting the King Khaled Hospital in Riyadh. The 14-bp indel was genotyped in the case and control groups. The frequency of the genotype +14/+14 was slightly higher in women with recurrent spontaneous abortions, but no significant differences were observed in the distribution of alleles and genotypes.
