Affiliations: [a] Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan | [b] Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan
Correspondence:
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Corresponding author: Rani Faryal, Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Fax: +92 51 9247006; E-mail:[email protected]
Abstract: BACKGROUND: Spleen Tyrosine Kinase (SYK) belongs to non-receptor
tyrosine Kinase family, which normally expresses in epithelial breast
tissues and acts as a tumor suppressor gene. OBJECTIVE: Analysis of mutations in the SYK gene and deregulation of
SYK transcripts by miRNA in breast cancer was studied. METHODS: All exons and exon/intron boundaries of SYK gene were
amplified and sequenced in blood samples of 207 breast cancer cases and 200
matched controls using PCR-single stranded conformational polymorphism
method. RESULTS: Sequence analysis revealed 10 novel mutations in breast
cancer patients. Among these 6 mutations (Ala 161Pro, His162Tyr, Phe191Tyr,
Val 535Gly, Ser 556lIe and Lys536Gln) were found in exonic region and 4
(26249 T>A, 63941 G>A, 63981G>C and 86548T>A) were found in intronic region.
All of these mutations are associated with ∼ 5 folds (p< 0.0001)
increase in breast cancer risk in present study cohort. Regulation of SYK
transcripts by miRNA was also analyzed using in silico bioinformatics tools,
exon 6's mutation (Phe191Tyr) was found to have altered interaction with miR-873. CONCLUSION: Overall novel mutations in SYK gene and in silico
analysis revealed that these mutations are crucial and might be responsible for altered
expression of SYK.
Keywords: SYK gene, spleen tyrosine kinase, mutations, microRNA, breast cancer
