Sequence changes in predicted promoter elements of STK11/LKB1 are unlikely to contribute to Peutz-Jeghers syndrome.
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.
Hearle
Nicholas C M
NC
Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK. nick.hearle@icr.ac.uk
Tomlinson
Ian
I
Lim
Wendy
W
Murday
Victoria
V
Swarbrick
Edwin
E
Lim
Guan
G
Phillips
Robin
R
Lee
Peter
P
O'Donohue
John
J
Trembath
Richard C
RC
Morrison
Patrick J
PJ
Norman
Andrew
A
Taylor
Rohan
R
Hodgson
Shirley
S
Lucassen
Anneke
A
Houlston
Richard S
RS
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
D004247:DNA; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases