Nature Genetics
15, 87 - 90 (1997)
doi:10.1038/ng0197-87
Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysisAkseli Hemminki1, Ian Tomlinson2, David Markie3, Heikki Järvinen4, Pertti Sistonen5, Anna-Maria Björkqvist1, Sakari Knuutila1, Reijo Salovaara6, Walter Bodmer2, Darryl Shibata7, Albert de la Chapelle1
& Lauri A. Aaltonen1, 8
1Departments of Medical Genetics, University of Helsinki, P. O. Box 21 (Haartmaninkatu 3), 00014 Helsinki, Finland.
2The Cancer Genetics Laboratory, Imperial Cancer Research Fund, P. O. Box 123, London WC2A 3PX, England, U.K.
3Department of Pathology, Dunedin School of Medicine, P.O. Box 913, Dunedin, New Zealand.
4Second Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4,00290 Helsinki, Finland.
5Finnish Red Cross Blood Transfusion Service, Kivihaantie 7,00310 Helsinki, Finland.
6Departments of Pathology, Haartman Institute, University of Helsinki, P. O. Box 21 (Haartmaninkatu 3), 00014 Helsinki, Finland.
7Department of Pathology, University of Southern California School of Medicine, 1200 N. State St. 736, Los Angeles, California 90033, USA.
8e-mail: Lauri.Aaltonen@Helsinki.Fi. 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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