Identification of novel SNPs in SYK gene of breast cancer patients: computational analysis of SNPs in the 5'UTR.
Spleen tyrosine kinase (SYK) is a non receptor type tyrosine kinase and a known candidate tumor suppressor gene in breast carcinoma. Loss of Syk is associated with breast cancer invasion and increased cell mortality. The main goal of our study was to detect germ-line polymorphisms in SYK gene in breast cancer affected females of Pakistani origin, in order to understand the genetic basis of complex human breast cancer. Seven novel SYK gene SNPs were identified in breast cancer patients. Among these, three were identified in intronic region, one at the 5'splice donor site (5'SD) and three in 5'untranslated region (5'UTR) of SYK gene. Mutations at the 5'SD and at 5'UTR can be crucial and could be responsible for generation of mutated Syk protein. In silico analysis of the 5'UTR variations revealed that one of the mutations was responsible for generation of a more stable structure of 5'UTR. Such a change in pre-mRNA could potentially down regulate SYK expression. These findings add to the growing literature implicating dysfunctional SYK gene as a contributor to human breast cancer, and suggest that therapies targeting its molecular pathways could provide effective means of treating/preventing breast cancer.
Molecular Medicine Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Islamabad, Pakistan.
Sehrish
S
Kanwal
Mahmood Akhtar
MA
Kayani
Rani
R
Faryal
D020121:5' Untranslated Regions; D000328:Adult; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D000072377:Syk Kinase
D020121:5' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase