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Two Distinct Amplified Regions at 17q11–q21 Involved in Human Primary Breast Cancer¹

Laboratoire d'Oncogénétique, Centre René Huguenin, 35 rue Dailly, F-92211 St-Cloud [I. B., R. L.], and Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, B P 163, 67404 Illkirch Cedex, C. U. de Strasbourg [C. T., C. H. R., C. M-L., M-C. R.), France

Chromosomal segment 17q11–q21 is a commonly amplified region in human breast carcinomas. Several lines of evidence suggest that ERBB2 is the gene responsible for the emergence of this amplicon, but four novel genes (called MLN 50, MLN 51, MLN 62, and MLN 64) in 17q11–q21 have recently been found to be amplified and overexpressed in breast cancer cell lines. We investigated 98 primary breast tumors for amplification of these five loci. Twenty-five tumors (25.5%) showed amplification of at least one of these markers, but most amplifications did not encompass all of the tested loci. The genes most frequently amplified were ERBB2 and MLN 64 (22 of 25 amplified cases). MLN 64 was always coamplified with ERBB2, and to a similar level. Amplification of these five genes always leads to overexpression of their mRNA; we observed no cases of overex-pression without amplification in any of these genes. Our results suggest that: (a) an independent, amplified region defined by MLN 62 (also called CART1 or TRAF4) is located in 17q11–q12; (b) in addition to ERBB2, MLN 64 is a major target for the 17q12-q21 amplicon; and (c) these MLN genes could be of pathogenetic significance in breast cancer.

¹ This work was supported by the Ligue Nationale de Lutte Contre le Cancer and the Comités Régionaux du Haut-Rhin, des Hauts de Seine, du Val d'Oise et des Yvelines, the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, the Centre Hospitalier Universitaire Régional, the Mutuelle Générale de l'Education Nationale, the Groupe de Recherches et d'Etudes sur les Génomes (Grant 94/50), the Association pour la Recherche sur le Cancer, the Fondation pour la Recherche Médicale Française, and the Fondation de France. R. L. is a research director with the Institut National de la Santé et de la Recherche Médicale.

² To whom requests for reprints should be addressed. Phone: 47-11-15-66; Fax: 47-11-16-96.

Received 6/ 3/96. Accepted 7/17/96.

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