title: Comparison of the prevalence of KRAS-LCS6 polymorphism (rs61764370) within different tumour types (colorectal, breast, non-small cell lung cancer and brain tumours). A study of the Czech population.
abstract: OBJECTIVE
  A germline SNP (rs61764370) is located in a let-7 complementary site (LCS6) in the 3'UTR of KRAS oncogene, and it was found to alter the binding capability of the mature let-7 microRNA to the KRAS mRNA. The aim of the study was to evaluate the frequency of the KRAS-LCS6 variant allele in different cancer types that included patients with colorectal cancer (CRC), breast cancer (BC), non-small cell lung cancer (NSCLC) and brain tumour patient subgroups from the Czech Republic. The occurrence of this genetic variant was correlated with the presence of selected somatic mutations representing predictive biomarkers in the respective tumours.
  
  
  METHODS
  DNA of tumour tissues was isolated from 428 colorectal cancer samples, 311 non-small cell lung cancer samples, 195 breast cancer samples and 151 samples with brain tumour. Analysis of SNP (rs61764370) was performed by the PCR+RFLP method and direct sequencing. KRAS, BRAF and EGFR mutation status was assessed using real-time PCR. The status of the HER2 gene was assessed using the FISH method.
  
  
  RESULTS
  The KRAS-LCS6 TG genotype has been detected in 16.4% (32/195) of breast cancer cases (in HER2 positive breast cancer 3.3%, in HER2 negative breast cancer 20.1%), in 12.4% (53/428) of CRC cases (KRAS/BRAF wild type CRC in 10.6%, KRAS mutant CRC in 10.1%, BRAF V600E mutant CRC in 18.5%), in 13.2% (41/311) of NSCLC samples, (EGFR mutant NSCLC patients in 8%, EGFR wild type NSCLC in 12.9%), and 17.9% (27/151) of brain tumour cases. The KRAS-LCS6 TG genotype was not significantly different across the studied tumours. In our study, the GG genotype has not been found among the cancer samples.
  
  
  CONCLUSIONS
  Based on the findings, it is concluded that the occurrence of the KRAS-LCS6 TG genotype was statistically significantly different in association with status of the HER2 gene in breast cancer. Furthermore, significant association between the mutation status of analysed somatic variants in genes of the EGFR signalling pathway (KRAS, BRAF, EGFR) and the KRAS-LCS6 genotype in colorectal cancer and NSCLC has not been established.
authors.affiliation: CGB laboratory, Ostrava, Czech Republic.|Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Ostrava.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Uvirova
authors.affiliation: CGB laboratory, Ostrava, Czech Republic.|Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Ostrava.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Simova
authors.affiliation: CGB laboratory, Ostrava, Czech Republic.|Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Ostrava.
authors.forename: Barbora
authors.initials: B
authors.lastname: Kubova
authors.affiliation: CGB laboratory, Ostrava, Czech Republic.|Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Ostrava.
authors.forename: Nina
authors.initials: N
authors.lastname: Dvorackova
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Ostrava.
authors.forename: Hana
authors.initials: H
authors.lastname: Tomaskova
authors.affiliation: Biopticka laboratory, Plzen.
authors.forename: Monika
authors.initials: M
authors.lastname: Sedivcova
authors.affiliation: CGB laboratory, Ostrava, Czech Republic.|Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Ostrava.
authors.forename: Petr
authors.initials: P
authors.lastname: Dite
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018153:Czech Republic / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate / Q000639:trends
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BRAF; FISH; KRAS; KRAS-LCS6; brain tumour; breast cancer; colorectal cancer; genotype; miRNA; non-small cell lung cancer; polymorphism