Genomic Profiling of Histological Special Types of Breast Cancer
Hugo M Horlings, Britta Weigelt, Maryou B Lambros, Eric M Anderson, Alan Mackay, Charlotte KY Ng, Felipe C Geyer, Marc J Van de Vijver, Jorge S Reis-Filho. Netherlands Cancer Institute, Amsterdam, Netherlands; Academic Medical Center, Amsterdam, Netherlands; Memorial Sloan-Kettering Cancer Center, New York, NY; Institute of Cancer Research, London, United Kingdom
Background: Whilst the majority of invasive breast cancers are classified as invasive carcinomas of no special type (IC-NST), up to 25% of cases are of a histological 'special type'. The aims of this study were to determine i) the constellation of gene copy number aberrations in histological special types of breast cancer, ii) whether these special breast cancer types are distinct from ER- and grade-matched IC-NSTs at the genomic level, and iii) the genes whose expression correlates with gene copy number in each histological special type.
Design: A series of 59 breast cancers of ten histological special types and a cohort of grade- and ER-matched IC-NSTs were subjected to microarray-based comparative genomic hybridisation (aCGH) and microarray-based gene expression profiling (Operon). An integrative analysis of aCGH and microarray-based gene expression profiles of the 59 special type breast cancers was performed.
Results: Hierarchical cluster analysis revealed that the patterns of gene copy number aberrations segregated with ER-status and histological grade, and that, in general, samples from each of the special types of breast cancer were preferentially allocated to one cluster. We confirmed the patterns of gene copy number aberrations previously reported for lobular, micropapillary, medullary, metaplastic and mucinous carcinomas. Metaplastic and medullary carcinomas were shown to have genomic profiles similar to those of IC-NST matched for grade and ER-status. The constellation of gene copy number aberrations found in invasive carcinomas with osteoclast-like stromal giant cells support the classification of this histological type as variant of IC-NSTs. Finally, integrative analysis of aCGH and gene expression data revealed copy number regulated genes and genes significantly overexpressed when amplified, including FOXM1 and FGF6 mapping to the 12p13.33-13.32 amplicon in metaplastic carcinomas.
Conclusions: Our results illustrate that together with histological grade and ER-status, histological type is also associated with the patterns and complexity of gene copy number aberrations in breast cancer.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 39, Wednesday Morning