title: Sequence changes in predicted promoter elements of STK11/LKB1 are unlikely to contribute to Peutz-Jeghers syndrome.
abstract: BACKGROUND
  Germline mutations or large-scale deletions in the coding region and splice sites of STK11/LKB1 do not account for all cases of Peutz-Jeghers syndrome (PJS). It is conceivable that, on the basis of data from other diseases, inherited variation in promoter elements of STK11/LKB1 may cause PJS.
  
  
  RESULTS
  Phylogenetic foot printing and transcription factor binding site prediction of sequence 5' to the coding sequence of STK11/LKB1 was performed to identify non-coding sequences of DNA indicative of regulatory elements. A series of 33 PJS cases in whom no mutation in STK11/LKB1 could be identified were screened for sequence changes in the putative promoter defined by nucleotides -1090 to -1472. Two novel sequence changes were identified, but were found to be present in healthy individuals.
  
  
  CONCLUSIONS
  These findings indicate that promoter sequence changes are unlikely to contribute to PJS.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK. nick.hearle@icr.ac.uk
authors.forename: Nicholas C M
authors.initials: NC
authors.lastname: Hearle
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Wendy
authors.initials: W
authors.lastname: Lim
authors.forename: Victoria
authors.initials: V
authors.lastname: Murday
authors.forename: Edwin
authors.initials: E
authors.lastname: Swarbrick
authors.forename: Guan
authors.initials: G
authors.lastname: Lim
authors.forename: Robin
authors.initials: R
authors.lastname: Phillips
authors.forename: Peter
authors.initials: P
authors.lastname: Lee
authors.forename: John
authors.initials: J
authors.lastname: O'Donohue
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Morrison
authors.forename: Andrew
authors.initials: A
authors.lastname: Norman
authors.forename: Rohan
authors.initials: R
authors.lastname: Taylor
authors.forename: Shirley
authors.initials: S
authors.lastname: Hodgson
authors.forename: Anneke
authors.initials: A
authors.lastname: Lucassen
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D001483:Base Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D018095:Germ-Line Mutation; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010580:Peutz-Jeghers Syndrome / Q000235:genetics*; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases