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Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis

Nature Genetics volume 15, pages 8790 (1997) | Download Citation



Many human cancer susceptibility genes have been successfully mapped by genetic linkage studies1. One that has so far eluded researchers is that for Peutz-Jeghers (P-J) syndrome, a condition characterized by intestinal hamartomatous polyposis and melanin spots of the lips, buccal mucosa and digits2,3. A dramatically elevated risk of malignancy has also been documented4. Gastrointestinal tumours as well as cancers of the breast, ovary, testis and uterine cervix appear to be overrepresented in families with this syndrome4,5. The nature of hamartomatous polyps is equivicol. Hamartomas are usually considered histologically benign6, but in the case of Peutz-Jeghers patients, there are reports of adenomatous and malignant changes in the polyps, and the possibility of a hamartoma-carcinoma sequence has been discussed5,7,8. A search for a putative tumour suppressor locus was made using comparative genomic hybridization (CGH) of Peutz-Jeghers polyps, combined with loss of heterozygosity (LOH) study. Genetic linkage analysis in 12 families using markers from a deletion site demonstrated the presence of a high-penetrance locus in distal 19p with a multipoint lod score of 7.00 at marker D19S886 without evidence of genetic heterogeneity. The study demonstrates the power of CGH combined with LOH analysis in identifying putative tumour suppressor loci, and provides molecular evidence of malignant potential in hamartomas.

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Author information


  1. Departments of Medical Genetics, University of Helsinki, P. O. Box 21 (Haartmaninkatu 3), 00014 Helsinki, Finland.

    • Akseli Hemminki
    • , Anna-Maria Björkqvist
    • , Sakari Knuutila
    • , Albert de la Chapelle
    •  & Lauri A. Aaltonen
  2. The Cancer Genetics Laboratory, Imperial Cancer Research Fund, P. O. Box 123, London WC2A 3PX, England, U.K.

    • Ian Tomlinson
    •  & Walter Bodmer
  3. Department of Pathology, Dunedin School of Medicine, P.O. Box 913, Dunedin, New Zealand.

    • David Markie
  4. Second Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4,00290 Helsinki, Finland.

    • Heikki Järvinen
  5. Finnish Red Cross Blood Transfusion Service, Kivihaantie 7,00310 Helsinki, Finland.

    • Pertti Sistonen
  6. Departments of Pathology, Haartman Institute, University of Helsinki, P. O. Box 21 (Haartmaninkatu 3), 00014 Helsinki, Finland.

    • Reijo Salovaara
  7. Department of Pathology, University of Southern California School of Medicine, 1200 N. State St. 736, Los Angeles, California 90033, USA.

    • Darryl Shibata


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Correspondence to Lauri A. Aaltonen.

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