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Identification of Germ-Line E-cadherin Mutations in Gastric Cancer Families of European Origin¹

Department of Oncology and Cancer Research Campaign Human Cancer Genetics Research Group, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom [S. A. G., K. L. G., S. J. R., D. H., N. G., B. A. J. P., C. C.]; Istituto Policattedra di Scienze Chirurgiche, Universita degli Studi di Sienna, 53100 Sienna, Italy [F. R., E. P.]; Instituto de Patologia e Imunologia Molecular da Universidade do Porto-IPATIMUP, 4200 Porto, Portugal [J. C. M., R. S.]; Molecular Pathology, Mayo Clinic, Rochester, Minnesota 55905 [K. H.]; Medical Genetics, Victoria General Hospital, Victoria, British Columbia V8Z 6R5, Canada [P. M.]; Department of Internal Medicine, The University of Virginia Health Sciences Center, Charlottesville, Virginia 22906-0013 [S. M. P.]; and Clinical and Molecular Genetics, Henry Ford Hospital, Detroit, Michigan 48202 [C. E. J.]

E-cadherin germ-line mutations have recently been described as a molecular basis for early-onset familial gastric cancer in Maori kindred. We screened 18 gastric cancer families of European origin for germ-line mutations to determine the proportion in which E-cadherin mutations occur and the clinical characteristics of the affected families. Truncating mutations were identified in three kindred with familial diffuse gastric cancer. In these families, the age of onset of gastric cancer was variable, the penetrance was incomplete, and one kindred contained individuals with cancers at other sites. Here, we show that a proportion of diffuse gastric cancer families of European origin have germ-line E-cadherin mutations; however, these mutations are absent in intestinal gastric cancer families.

¹ This study was funded by the Cancer Research Campaign (CRC) and by a grant from the Cambridge Cancer Research Fund. K. L. G. is a recipient of an Overseas Research Students award, a Prince of Wales Scholarship from the Cambridge Commonwealth Trust, and a Sackler Studentship; D. H. is the recipient of a McLaughlin Fellowship; C. E. J. is supported by grants from the McGraw Foundation and the Detroit San Marino Club; and B. A. J. P. is a Gibb Fellow of the Cancer Research Campaign.

² The first three authors contributed equally to this study.

³ To whom requests for reprints should be addressed, Phone: 44-1223-331989; Fax: 44-1223-331753; E-mail: cc234@cam.ac.uk.

Received 6/26/98. Accepted 7/31/98.

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