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Previous Volume 344:1904-1909 June 21, 2001 Number 25 Next

	Full Text PDF Editorial by Weitzel, J. N. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Germ-line truncating mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer. These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance, predominantly in young persons. We describe genetic screening, surgical management, and pathological findings in young persons with truncating mutations in CDH1 from two unrelated families with hereditary diffuse gastric cancer.

Methods Mutation-specific predictive genetic testing was performed by polymerase-chain-reaction amplification, followed by restriction-enzyme digestion and DNA sequencing in Family 1 and by heteroduplex analysis in Family 2. A total gastrectomy was performed prophylactically in five carriers of mutations who were between 22 and 40 years old. In each case, the entire mucosa of the stomach was extensively sampled for microscopical analysis.

Results Superficial infiltrates of malignant signet-ring cells were identified in the surgical samples from all five persons who underwent gastrectomy. These early diffuse gastric cancers were multifocal in three of the five cases, and in one person infiltrates of malignant signet-ring cells were present in 65 of the 140 tissue blocks analyzed, representing in aggregate less than 2 percent of the gastric mucosa.

Conclusions We recommend genetic counseling and consideration of prophylactic gastrectomy in young, asymptomatic carriers of germ-line truncating CDH1 mutations who belong to families with highly penetrant hereditary diffuse gastric cancer.

Source Information

From the Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver (D.G.H., P.M.M.); the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver (D.G.H.); the Sections of Medical Genetics (P.M.M.), Surgery (A.H.), and Pathology (R.M.), Victoria General Hospital, Victoria, B.C. — all in Canada; the Instituto de Patalogia e Imunologia Molecular and the Faculty of Medicine, University of Porto, Porto, Portugal (F.C., R.S.); the Departments of Surgery (F.R.L.) and Medical Genetics (K.G.M., C.E.J.), Henry Ford Hospital, Detroit; and the Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom (D.G.H., C.C.).

Address reprint requests to Dr. Huntsman at the Department of Pathology, British Columbia Cancer Agency, 600 W. 10th Ave., Vancouver, BC V5Z 1L3, Canada, or at dhuntsma{at}bccancer.bc.ca, or to Dr. Caldas at the Department of Oncology, University of Cambridge, Wellcome Trust/MRC Bldg., Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom, or at cc234{at}cam.ac.uk.

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