Germline mutations of the STK11 gene in Korean Peutz-Jeghers syndrome patients

Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease c haracterized by hamartomatous gastrointestinal polyps and mucocutaneous pig mentation, with an increased risk for various neoplasms, including gastroin testinal cancer. Recently, the PJS gene encoding the serine/threonine kinas e STK11 (also named LKB1) was mapped to chromosome 19p13.3, and germline mu tations were identified in PJS patients. We screened a total of ten Korean PJS patients (nine sporadic cases and one familial case including two patie nts) to investigate the germline mutations of the STK11 gene. By polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing analysis, three kinds of mis-sense mutation and a frame-shift mutation were identified: codon 232 (TCC to CCC) in exon 5, codon 256 (GAA to GCA) in ex on 6, codon 324 (CCG to CTG) in exon 8, and a guanine insertion at codon 34 2 resulting in a premature stop codon in exon 8. These mis-sense variants w ere not detected in 100 control DNA samples. Furthermore, we found an intro nic mutation at the dinucleotide sequence of a splice-acceptor site: a one base substitution from AG to CG in intron 1, which may cause aberrant splic ing. Most reported germline mutations of the STK11 gene in PJS patients wer e frame-shift or non-sense mutations resulting in truncated proteins. Toget her, these findings indicate that germline mis-sense mutations of the STK11 gene are found in PJS patients in addition to truncating mutations. The ef fects of these mutations on protein function require further examination. I n summary, we found germline mutations of the STK11 gene in five out of ten Korean PJS patients. (C) 2000 Cancer Research Campaign.