PURPOSE: Since the identification of BRCA1 and BRCA2, there has been no major breast cancer susceptibility gene discovered by linkage analysis in breast cancer families. This has been attributed to the heterogeneous genetic basis for the families under study. Recent studies have indicated that breast tumors arising in women carrying a BRCA1 mutation have distinct histopathologic, immunophenotypic, and genetic features. To a lesser extent, this is also true for breast tumors from BRCA2 carriers. This indicates that it might be possible to decrease the genetic heterogeneity among families in which BRCA1 and BRCA2 have been excluded with high certainty (BRCAx families) if distinct subgroups of BRCAx-related breast tumors could be identified. EXPERIMENTAL DESIGN: Loss of heterozygosity (LOH) analysis with at least one marker per chromosomal arm (65 markers) was used to characterize 100 breast tumors derived from 92 patients from 42 selected BRCAx families. In addition, the immunophenotype of 10 markers was compared with that of 31 BRCA1- and 21 BRCA2-related breast tumors. RESULTS AND CONCLUSIONS: The BRCAx-related tumors were characterized by more frequent LOH at 22q relative to sporadic breast cancer (P < 0.02), and differed significantly from BRCA1- and BRCA2-related tumors in their positivity for Bcl2. However, cluster analyses of the combined data (LOH and immunohistochemistry) did not result in subgroups that would allow meaningful subclassification of the families. On chromosomes 2, 3, 6, 12, 13, 21, and 22, we found markers at which LOH occurred significantly more frequent among the tumors from patients belonging to a single family than expected on the basis of overall LOH frequencies. Nonetheless, linkage analysis with markers for the corresponding regions on chromosomes 12, 21, and 22 did not reveal significant logarithm of the odds.
PURPOSE: Since the identification of BRCA1 and BRCA2, there has been no major breast cancer susceptibility gene discovered by linkage analysis in breast cancer families. This has been attributed to the heterogeneous genetic basis for the families under study. Recent studies have indicated that breast tumors arising in women carrying a BRCA1 mutation have distinct histopathologic, immunophenotypic, and genetic features. To a lesser extent, this is also true for breast tumors from BRCA2 carriers. This indicates that it might be possible to decrease the genetic heterogeneity among families in which BRCA1 and BRCA2 have been excluded with high certainty (BRCAx families) if distinct subgroups of BRCAx-related breast tumors could be identified. EXPERIMENTAL DESIGN: Loss of heterozygosity (LOH) analysis with at least one marker per chromosomal arm (65 markers) was used to characterize 100 breast tumors derived from 92 patients from 42 selected BRCAx families. In addition, the immunophenotype of 10 markers was compared with that of 31 BRCA1- and 21 BRCA2-related breast tumors. RESULTS AND CONCLUSIONS: The BRCAx-related tumors were characterized by more frequent LOH at 22q relative to sporadic breast cancer (P < 0.02), and differed significantly from BRCA1- and BRCA2-related tumors in their positivity for Bcl2. However, cluster analyses of the combined data (LOH and immunohistochemistry) did not result in subgroups that would allow meaningful subclassification of the families. On chromosomes 2, 3, 6, 12, 13, 21, and 22, we found markers at which LOH occurred significantly more frequent among the tumors from patients belonging to a single family than expected on the basis of overall LOH frequencies. Nonetheless, linkage analysis with markers for the corresponding regions on chromosomes 12, 21, and 22 did not reveal significant logarithm of the odds.
Authors: Bradley Downs; Fengxia Xiao; Yeong C Kim; Pei Xian Chen; Dali Huang; Elizabeth A Fleissner; Kenneth Cowan; San Ming Wang Journal: Breast J Date: 2017-01-24 Impact factor: 2.431
Authors: Robert M W Hofstra; Amanda B Spurdle; Diana Eccles; William D Foulkes; Niels de Wind; Nicoline Hoogerbrugge; Frans B L Hogervorst Journal: Hum Mutat Date: 2008-11 Impact factor: 4.878
Authors: Juan Manuel Rosa-Rosa; Guillermo Pita; Miguel Urioste; Gemma Llort; Joan Brunet; Conxi Lázaro; Ignacio Blanco; Teresa Ramón y Cajal; Orland Díez; Miguel de la Hoya; Trinidad Caldés; Maria-Isabel Tejada; Anna González-Neira; Javier Benítez Journal: Am J Hum Genet Date: 2009-01-15 Impact factor: 11.025
Authors: Dirce Maria Carraro; Maria Aparecida Azevedo Koike Folgueira; Bianca Cristina Garcia Lisboa; Eloisa Helena Ribeiro Olivieri; Ana Cristina Vitorino Krepischi; Alex Fiorini de Carvalho; Louise Danielle de Carvalho Mota; Renato David Puga; Maria do Socorro Maciel; Rodrigo Augusto Depieri Michelli; Eduardo Carneiro de Lyra; Stana Helena Giorgi Grosso; Fernando Augusto Soares; Maria Isabel Alves de Souza Waddington Achatz; Helena Brentani; Carlos Alberto Moreira-Filho; Maria Mitzi Brentani Journal: PLoS One Date: 2013-03-01 Impact factor: 3.240
Authors: Petra E A Huijts; Maaike P G Vreeswijk; Karin H G Kroeze-Jansema; Catharina E Jacobi; Caroline Seynaeve; Elly M M Krol-Warmerdam; Pauline M Wijers-Koster; Jannet C Blom; Karen A Pooley; Jan G M Klijn; Rob A E M Tollenaar; Peter Devilee; Christi J van Asperen Journal: Breast Cancer Res Date: 2007 Impact factor: 6.466