title: Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast.
abstract: Alterations in the gene expression profile in epithelial cells during breast ductal carcinoma (DC) progression have been shown to occur mainly between pure ductal carcinoma in situ (DCIS) to the in situ component of a lesion with coexisting invasive ductal carcinoma (DCIS-IDC) implying that the molecular program for invasion is already established in the preinvasive lesion. For assessing early molecular alterations in epithelial cells that trigger tumorigenesis and testing them as prognostic markers for breast ductal carcinoma progression, we analyzed, by reverse transcription-quantitative polymerase chain reaction, eight genes previously identified as differentially expressed between epithelial tumor cells populations captured from preinvasive lesions with distinct malignant potential, pure DCIS and the in situ component of DCIS-IDC. ANAPC13 and CLTCL1 down-regulation revealed to be early events of DC progression that anticipated the invasiveness manifestation. Further down-regulation of ANAPC13 also occurred after invasion appearance and the presence of the protein in invasive tumor samples was associated with higher rates of overall and disease-free survival in breast cancer patients. Furthermore, tumors with low levels of ANAPC13 displayed increased copy number alterations, with significant gains at 1q (1q23.1-1q32.1), 8q, and 17q (17q24.2), regions that display common imbalances in breast tumors, suggesting that down-regulation of ANAPC13 contributes to genomic instability in this disease.
authors.affiliation: Laboratory of Genomics and Molecular Biology, International Center of Research and Teaching, A.C. Camargo Hospital, São Paulo, SP, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sens-Abuázar
authors.forename: Elisa
authors.initials: E
authors.lastname: Napolitano E Ferreira
authors.forename: Cynthia Aparecida Bueno Toledo
authors.initials: CA
authors.lastname: Osório
authors.forename: Ana Cristina Victorino
authors.initials: AC
authors.lastname: Krepischi
authors.forename: Tatiana Iervolino
authors.initials: TI
authors.lastname: Ricca
authors.forename: Nadia Pereira
authors.initials: NP
authors.lastname: Castro
authors.forename: Isabela Werneck
authors.initials: IW
authors.lastname: da Cunha
authors.forename: Maria do Socorro
authors.initials: Mdo S
authors.lastname: Maciel
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
authors.forename: Maria Mitzi
authors.initials: MM
authors.lastname: Brentani
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro