title: Impact of 3'UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population.
abstract: OBJECTIVE
  Several studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3' untranslated region (3'UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3'UTR regions of the KRAS gene and the effect of KRAS 3'UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT.
  
  
  METHODS
  Codons 12, 13, and 61 and 3'UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients.
  
  
  RESULTS
  We defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3'UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required.
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey. Electronic address: egeli@uludag.edu.tr.
authors.forename: Unal
authors.initials: U
authors.lastname: Egeli
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Secil
authors.initials: S
authors.lastname: Ak
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Gulsah
authors.initials: G
authors.lastname: Cecener
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Berrin
authors.initials: B
authors.lastname: Tunca
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Gulcin
authors.initials: G
authors.lastname: Tezcan
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Elif Demirdogen
authors.initials: ED
authors.lastname: Sevinc
authors.affiliation: Department of General Surgery, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Ekrem
authors.initials: E
authors.lastname: Kaya
authors.affiliation: Department of General Surgery, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Halit Ziya
authors.initials: HZ
authors.lastname: Dundar
authors.affiliation: Department of General Surgery, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Pinar
authors.initials: P
authors.lastname: Sarkut
authors.affiliation: Department of General Surgery, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Ozen
authors.affiliation: Department of General Surgery, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Ozkan
authors.initials: O
authors.lastname: Balcin
authors.affiliation: Department of Medical Oncology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Turkkan
authors.initials: T
authors.lastname: Evrensel
authors.affiliation: Department of Pathology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Omer
authors.initials: O
authors.lastname: Yerci
authors.affiliation: Department of Pathology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Nesrin
authors.initials: N
authors.lastname: Ugras
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001661:Biliary Tract Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D014421:Turkey / Q000453:epidemiology; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D003062:Codon; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: 3′ untranslated region; Codon 13; Invasion; KRAS; Mutation