title: Variants of the PPARD gene and their clinicopathological significance in colorectal cancer.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor delta (PPARD) is nuclear hormone receptor involved in colorectal cancer (CRC) differentiation and progression. The purpose of this study was to determine prevalence and spectrum of variants in the PPARD gene in CRC, and their contribution to clinicopathological endpoints.
  
  
  RESULTS
  Direct sequencing of the PPARD gene was performed in 303 primary tumors, in blood samples from 50 patients with ≥ 3 affected first-degree relatives, 50 patients with 2 affected first-degree relatives, 50 sporadic patients, 360 healthy controls, and in 6 colon cancer cell lines. Mutation analysis revealed 22 different transversions, 7 of them were novel. Three of all variants were somatic (c.548A>G, p.Y183C, c.425-9C>T, and c.628-16G>A). Two missense mutations (p.Y183C and p.R258Q) were pathogenic using in silico predictive program. Five recurrent variants were detected in/adjacent to the exons 4 (c.1-87T>C, c.1-67G>A, c.130+3G>A, and c.1-101-8C>T) and exon 7 (c.489T>C). Variant c.489C/C detected in tumors was correlated to worse differentiation (P = 0.0397).
  
  
  CONCLUSIONS
  We found 7 novel variants among 22 inherited or acquired PPARD variants. Somatic and/or missense variants detected in CRC patients are rare but indicate the clinical importance of the PPARD gene.
authors.affiliation: Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, County Council of Östergötland, University of Linköping, Linköping, Sweden.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ticha
authors.affiliation: Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, County Council of Östergötland, University of Linköping, Linköping, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gnosa
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Lindblom
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, County Council of Östergötland, University of Linköping, Linköping, Sweden.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Sun
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D047494:PPAR delta / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D047494:PPAR delta