Article Text

Download PDFPDF
STK11 genotyping and cancer risk in Peutz-Jeghers syndrome
  1. V Schumacher1,
  2. T Vogel2,
  3. B Leube1,
  4. C Driemel3,
  5. T Goecke1,
  6. G Möslein3,
  7. B Royer-Pokora1
  1. 1Institute of Human Genetics and Anthropology, University of Düsseldorf, Universitaetsstrasse 1, 40225 Düsseldorf, Germany
  2. 2Department of Traumatological Surgery, University of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany
  3. 3Department of General and Visceral Surgery, University of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany
  1. Correspondence to:
 Dr. Valérie Schumacher
 Heinrich-Heine Universitaet Düsseldorf, Institut für Humangenetik und Anthropologie, Universitaetsstrasse 1, D-40225 Düsseldorf;

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Peutz-Jeghers syndrome (PJS; OMIM #175200) is an autosomal dominant disorder characterised by mucocutaneous melanin pigmentation, gastrointestinal hamartomatous polyposis, and an increased risk for the development of various neoplasms.1,2 Malignancies occur both in the gastrointestinal tract and in extraintestinal sites such as the pancreas, the breast, and reproductive organs. The estimated relative cancer risk may be 15 fold higher than in the general population1 and appears to be particularly high in women (20 fold) because of an increased risk of development of breast cancer and gynaecological malignancies.2

Germline mutations in the STK11/LKB1 gene on 19p13.3 are found in 30–70% of PJS cases, depending on the screening method, with considerable uncharacterised genetic heterogeneity remaining in this syndrome.3,4 The disease causing gene has been identified by two independent groups.5,6 Human STK11 encodes a serine/threonine protein kinase that is highly homologous to the mouse protein Lkb1 and the Xenopus kinase XEEK1,7,8 and is expressed in all human tissues.9 The kinase domain of the human 433 amino acid protein is localised between residues 49 and 309,7 and shows homology to the conserved catalytic core of the kinase domain common to both serine/threonine and tyrosine protein kinase family members.10 Most mutations found in PJS patients are small deletions/insertions or single base substitutions leading to an abnormal truncated/kinase inactive protein.

Loss of the wild type allele in hamartomas and adenocarcinomas occurring in patients with PJS suggests that STK11 is a tumour suppressor gene. Several studies have described a role in cell cycle arrest,11 p53 mediated apoptosis,12 Wnt signalling,13,14 TGF-β signalling,15 Ras induced cell transformation,16 and cell polarity.17–20 Growth suppression requires phosphorylation of STK1121,22 and was found to be caused by activation of the CDK …

View Full Text


  • Competing interests: none declared

  • This work is dedicated to Professor Dr med. h.c. F. Vogel