This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sobol, H. Articles by Birnbaum, D. Search for Related Content PubMed PubMed Citation Articles by Sobol, H. Articles by Birnbaum, D.

Truncation at Conserved Terminal Regions of BRCA1 Protein Is Associated with Highly Proliferating Hereditary Breast Cancers¹

Department of Genetic Oncology and Laboratory of Tumor Biology [H.S., F.K., T.N., F.E., D. B.], Department of Pathology [J. J.], Paoli-Calmettes Institute, 232 Boulevard Sainte Marguerite, 13273 Marseille Cedex 9; INSERM U 119, 27 Bd Leï Roure, 13009 Marseille [D. B.]; Unit of Genetic Oncology, Curie Institute, 75231 Paris Cedex 05 [D. S-L.]; Departments of Clinical Biology [B. B-de-P.], Medicine [N. J.], and Pathology [J-M. G.], Gustave Roussy Institute, 94805 Villejuif Cedex; and Laboratory of Human Molecular Oncology, Oscar Lambret Center [J-P. P.], 59020 Lille Cedex, France

The existence of two subgroups of BRCA1-associated breast cancer (BC) families has been recently posited: the first with highly proliferating tumors, and the second composed of cases with a low proliferation rate. Our aim was to test whether the proliferation rate of BRCA1-associated breast cancers was affected by the site of the germ line mutation in the BRCA1 gene. We analyzed the distribution of the mitotic index, a histoprognostic grade component shown to segregate in families, matching for germ line mutation location in a series of 28 breast cancers from 20 kindreds. We observed a prevalence of highly proliferating tumors when the mutation occurs in the two terminal conserved domains of the BRCA1 protein, i.e., in the amino and carboxyl termini (P = 0.0024). Our data provide evidence for a genotype-phenotype correlation and along with their strong conservation during evolution argue for the importance of these two regions in the control of mammary cell growth.

¹ This work was supported by Paoli-Calmettes Institute, INSERM, and grants from Projet Hospitalier de Recherche Clinique, La Ligue Nationale Contre le Cancer (the national office and the district committees of Alpes de Haute Provence, Bouches du Rhône, Corse du Sud, Haute Corse, Nord, Var), Caisse Nationale d'Assurance Maladie, Federation Nationale des Groupements des Entreprises Francaises dans la Lutte contre le Cancer, Groupements Des Entreprises Francaises Dans la Lutte contre le Cancer Association pour la Recherche sur le Cancer, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupement de Recherche et d'Etude sur les Génomes.

² To whom requests for reprints should be addressed. Phone: (33) 91 22 35 40; Fax: (33) 91 22 35 04.

Received 3/27/96. Accepted 4/17/96.

This article has been cited by other articles:

				C. Osborne, P. Wilson, and D. Tripathy Oncogenes and Tumor Suppressor Genes in Breast Cancer: Potential Diagnostic and Therapeutic Applications Oncologist, July 1, 2004; 9(4): 361 - 377. [Abstract] [Full Text] [PDF]

				P. Hohenstein and R. Fodde Of mice and (wo)men: genotype-phenotype correlations in BRCA1 Hum. Mol. Genet., October 15, 2003; 12(90002): R271 - 277. [Abstract] [Full Text] [PDF]

				J. M. Satagopan, K. Offit, W. Foulkes, M. E. Robson, S. Wacholder, C. M. Eng, S. E. Karp, and C. B. Begg The Lifetime Risks of Breast Cancer in Ashkenazi Jewish Carriers of BRCA1 and BRCA2 Mutations Cancer Epidemiol. Biomarkers Prev., May 1, 2001; 10(5): 467 - 473. [Abstract] [Full Text]

				F. Durocher, J. Simard, J. Ouellette, V. Richard, F. Labrie, and G. Pelletier Localization of BRCA1 Gene Expression in Adult Cynomolgus Monkey Tissues J. Histochem. Cytochem., September 1, 1997; 45(9): 1173 - 1188. [Abstract] [Full Text] [PDF]