title: Novel SYK gene variations and changes in binding sites of miRs in breast cancer patients.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.|Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: R
authors.initials: R
authors.lastname: Faryal
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: M
authors.initials: M
authors.lastname: Ishfaq
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: T
authors.initials: T
authors.lastname: Hayat
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: I
authors.initials: I
authors.lastname: Mahjabeen
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: M A
authors.initials: MA
authors.lastname: Kayani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D000072377:Syk Kinase / Q000235:genetics*; D055815:Young Adult
chemical_list: D035683:MicroRNAs; C000606896:SYK protein, human; D000072377:Syk Kinase
keywords: SYK gene; breast cancer; microRNA; mutations; spleen tyrosine kinase