Abstract
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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References
Knudson, A.G. All in the (cancer) family. Nature Genet. 5, 103–104 (1993).
Peutz, J.L. On a very remarkable case of familial polyposis of the mucous membrane of the intestinal tract and nasopharynx accompanied by peculiar pigmentation of the skin and mucous membrane. Ned. Tijdschr. Geneeskd. 10, 134–146 (1921).
Jeghers, H., McKusick, V.A. & Katz, K.H. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits: a syndrome of diagnostic significance. N. Engl. J. Med. 241, 992–1005 (1949).
Giardiello, P.M. et al. Increased risk of cancer in the Peutz-Jeghers sydrome. N. Engl. J. Med. 316, 1511–1514 (1987).
Phillips, R.K.S., Spigelman, A.D. & Thomson, J.P.S. S. (eds.) Familial adenomatous polyposis and other polyposis syndromes(Edward Arnold, London, England, 1994).
Rosai, J. (ed.) Ackerman's surgical pathology(8th ed. Mosby, St Louis, Missouri, USA, 1996).
Hizawa, K. et al. Neoplastictransformation arising in Peutz-Jeghers polyposis. Dis. Colon Rectum. 36, 953–957 (1993).
Defago, M.R. et al. Carcinoma in situ arising in a gastric hamartomatous polyp in a patient with Peutz-Jeghers syndrome. Endoscopy. 28, 267 (1996).
Kallioniemi, A. et al. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumours. Science. 258, 818–821 (1992).
Kallioniemi, O.-P. et al. Optimizing comparative genetic hybridization for analysis of DNA sequence copy number changes in solid tumours. Genes Chrom. Cancer. 10, 231–243 (1994).
Shibata, D., Navidi, W., Salovaara, R., Li, Z.-H. & Aaltonen, L.A. Somatic microsatellite mutations as molecular tumour clocks. Nature Med. 2, 676–681 (1996).
Ott, J. Analysis of human genetic linkage (The Johns Hopkins University Press, Baltimore, Maryland, USA. 1991).
Shibata, D. et al. Specific genetic analysis of microscopic tissue after selective ultraviolet radiation fractionation and the polymerase chain reaction. Am. J. Pathol. 14, 539–543 (1992).
The Genethon database, http://www.genethon.fr, ftp://ftp.genethon.fr
The Genome Database, http://gdbwww.gdb.org
Cottingham, R.W. Jr., Idury, R.M. & Schäffer, A.A. Faster sequential genetic linkage computations. Am. J. Hum. Genet. 53, 252–263 (1993).
The CEPH database, http://www.cephb.fr
O'Connell, J.R. & Weeks, D.E. The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set-recording and fuzzy inheritance. Nature Genet. 11, 402–408 (1995).
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Hemminki, A., Tomlinson, I., Markie, D. et al. Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nat Genet 15, 87–90 (1997). https://doi.org/10.1038/ng0197-87
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DOI: https://doi.org/10.1038/ng0197-87
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