Abstract
Peutz–Jeghers syndrome (PJS) is an autosomal dominantly inherited disease characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation, with an increased risk for various neoplasms, including gastrointestinal cancer. Recently, the PJS gene encoding the serine/threonine kinase STK11 (also named LKB1) was mapped to chromosome 19p13.3, and germline mutations were identified in PJS patients. We screened a total of ten Korean PJS patients (nine sporadic cases and one familial case including two patients) 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 exon 6, codon 324 (CCG to CTG) in exon 8, and a guanine insertion at codon 342 resulting in a premature stop codon in exon 8. These mis-sense variants were not detected in 100 control DNA samples. Furthermore, we found an intronic 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 splicing. Most reported germline mutations of the STK11 gene in PJS patients were frame-shift or non-sense mutations resulting in truncated proteins. Together, these findings indicate that germline mis-sense mutations of the STK11 gene are found in PJS patients in addition to truncating mutations. The effects of these mutations on protein function require further examination. In summary, we found germline mutations of the STK11 gene in five out of ten Korean PJS patients. © 2000 Cancer Research Campaign
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References
Dong SM, Kim KM, Kim SY, Shin MS, Na EY, Lee SH, Park WS, Yoo NJ, Jang JJ, Yoon CY, Kim JW, Kim SY, Yang YM, Kim SH, Kim CS and Lee JY (1998) Frequent somatic mutations in serine/threonine kinase 11/Peutz–Jeghers syndrome gene in left-sided colon cancer. Cancer Res 58: 3787–3790
Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV, Krush AJ, Yardley JH and Luk GD (1987) Increased risk of cancer in the Peutz–Jeghers syndrome. N Engl J Med 11: 1511–1514
Gruber SB, Entius MM, Petersen GM, Laken SJ, Longo PA, Boyer R, Levin AM, Mujumda UJ, Trent JM, Kinzler KW, Vogelstein B, Hamilton SR, Polymeropoulos MH, Offerhaus GJ and Giardiello FM (1998) Pathogenesis of adenocarcinoma in Peutz–Jeghers syndrome. Cancer Res 58: 5267–5270
Guldberg P, thor Straten P, Ahrenkiel V, Seremet T, Kirkin AF and Zeuthen J (1999) Somatic mutation of the Peutz–Jeghers syndrome gene, LKB1/STK11, in malignant melanoma. Oncogene 18: 1777–1780
Hemminki A (1999) The molecular basis and clinical aspects of Peutz–Jeghers syndrome. Cell Mol Life Sci 55: 735–750
Hemminki A, Tomlinson I, Markie D, Jarvinen H, Sistonen P, Bjorkqvist AM, Knuutila S, Salovaara R, Bodmer W, Shibata D, Chapelle A and Aaltonen LA (1997) Localization of a susceptibility locus for Peutz–Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nat Genet 15: 87–90
Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, Bignell G, Warren W, Aminoff M, Hoglund P, Jarvinen H, Kristo P, Pelin K, Ridanpaa M, Salovaara R, Toro T, Bodmer W, Olschwang S, Olsen AS, Stratton MR, Chapelle A and Aaltonen LA (1998) A serine/threonine kinase gene defective in Peutz–Jeghers syndrome. Nature 391: 184–187
Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, Muller O, Back W and Zimmer M (1998) Peutz–Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 18: 38–44
Nakagawa H, Koyama K, Miyoshi Y, Ando H, Baba S, Watatani M, Monden M and Nakamura Y (1998) Nine novel germline mutations of STK11 in ten families with Peutz–Jeghers syndrome. Hum Genet 103: 168–172
Park WS, Moon YW, Yang YM, Kim YS, Kim YD, Fuller BG, Vortmeyer AO, Fogt F, Lubensky IA and Zhuang Z (1998) Mutations of the STK11 gene in sporadic gastric carcinoma. Int J Oncol 13: 601–604
Smith DP, Spicer J, Smith A, Swift S and Ashworth A (1999) The mouse Peutz–Jeghers syndrome gene Lkb1 encodes a nuclear protein kinase. Hum Mol Genet 8: 1479–1485
Spigelman AD, Murday V and Phillips RK (1989) Cancer and the Peutz–Jeghers syndrome. Gut 30: 1588–1590
Su JY, Erikson E and Maller JL (1996) Cloning and characterization of a novel serine/threonine protein kinase expressed in early Xenopus embryos. J Biol Chem 271: 14430–14437
Westerman AM, Entius MM, Boor PPC, Koole R, Baar E, Offerhaus GJA, Lubinski J, Lindhout D, Halley DJJ, Rooij FWM and Wilson JHP (1999) Novel mutations in the LKB1/STK11 gene in Dutch Peutz–Jeghers families. Hum Mutat 13: 476–481
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Yoon, KA., Ku, JL., Choi, H. et al. Germline mutations of the STK11 gene in Korean Peutz–Jeghers syndrome patients. Br J Cancer 82, 1403–1406 (2000). https://doi.org/10.1054/bjoc.1999.1125
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DOI: https://doi.org/10.1054/bjoc.1999.1125