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Genome-wide Search for Loss of Heterozygosity Shows Extensive Genetic Diversity of Human Breast Carcinomas¹

Laboratoire de Biologie des Tumeurs and CR Inserm 4U003C, Institut Paoli-Calmettes, 13273 Marseille Cédex 9 [F. K., T. N., F. A., V. W., J. G., H. S., D. B.]; U.119 Inserm, 13009 Marseille [F. C., D. B.]; Département d'Anatomie-pathologique, Institut Paoli-Calmettes, Marseille, France [J. J.]; Institut Bergonité, 33076 Bordeaux [M. L.]; Centre Val D'Aurelle-Paul Lamarque, Montpellier, France [J. S-L.]; and Département d'Oncogénétique, Institut Paoli-Calmettes, Marseille [H. S., F. E.], France

Deletions of genomic regions involving tumor suppressor genes are thought to be important in the initiation and progression of breast cancer. We conducted a genome-wide search for deleted regions in a series of 75 human breast carcinomas by studying the allelic patterns of 184 microsatellite markers distributed over all chromosomes and looking for loss of heterozygosity (LOH). We identified 56 regions of consistent LOH. Strikingly, every tumor had a different set of deletions. To study this complexity, we applied a phylogenetic-like type of analysis. Each region was involved in a certain proportion of tumors, ranging from 20 to 62%; the most frequently involved regions were on chromosome arms 8p, 11q, 16q, and 17p. There was a correlation (P = 0.005) between the level of LOH and the size of the tumors. Tumors with a high level of LOH were also highly proliferative and had a high mitotic index.

¹ This work was supported by Institut Paoli-Calmettes, Inserm (CRI 9703), and grants from Association pour la Recherche sur le Cancer, Comité National and Comités des Bouches-du-Rhône, des Alpes de Haute-Provence et du Var de la Ligue Nationale Contre le Cancer, Federation des Groupements des Enterprises Françaises pour la Lutte contre le Cancer, and Fédération Nationale des Centres de Lutte Contre le Cancer.

² To whom requests for reprints should be addressed, at U.119 Inserm, 27 Bd. Leï Roure, 13009 Marseille, France. Phone: 33 4 91 74 84 07; Fax: 33 4 91 26 03 64; E-mail: birnbaum@marseille.inserm.fr.

Received 4/11/97. Accepted 10/28/97.

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