STK11 genotyping and cancer risk in Peutz-Jeghers syndrome

• Published in: Journal of medical genetics Vol. 42; no. 5; pp. 428 - 435
• Main Authors: Schumacher, V, Vogel, T, Leube, B, Driemel, C, Goecke, T, Möslein, G, Royer-Pokora, B
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.05.2005; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adolescent; Adult; Aged; Apoptosis; Biological and medical sciences; Breast cancer; Cardiology. Vascular system; Cell cycle; Child; Child, Preschool; Deoxyribonucleic acid; Dermatology; DNA; DNA Mutational Analysis; familial cancer syndrome; Family medical history; functional protein domains; General aspects. Genetic counseling; Genetic Predisposition to Disease; Genetic Testing; Genotype; genotype-phenotype correlation; Humans; Kinases; Letter to JMG; Medical genetics; Medical sciences; Middle Aged; Mutation; Neoplasms - genetics; Patients; Peutz-Jeghers Syndrome - complications; Peutz-Jeghers Syndrome - diagnosis; Peutz-Jeghers Syndrome - genetics; Phosphorylation; Pigmentary diseases of the skin; Protein-Serine-Threonine Kinases - genetics; Proteins; Studies; tumour suppressor gene; Human; Peutz Jeghers syndrome; Skin disease; Pigmentation disorder; Lentiginosis; Genotype; Risk; Malignant tumor; Polyposis; Genetic disease; Risk factor; Digestive diseases; Genetics; Benign neoplasm
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2004.026294

The estimated relative cancer risk may be 15 fold higher than in the general population 1 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. PJS is a cancer predisposing disorder; however, cancer risk may vary. [...]we studied whether specific STK11 mutations may confer a lower or higher cancer risk in PJS patients by examining the site and type of mutations with regard to cancer frequency and cancer type.