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We analysed chromosome 16q in 106 breast cancers using tiling-path array-comparative genomic hybridization (aCGH). About 80% of ductal cancers (IDCs) and all lobular cancers (ILCs) lost at least part of 16q. Grade I (GI) IDCs and ILCs often lost the whole chromosome arm. Grade II (GII) and grade III (GIII) IDCs showed less frequent whole-arm loss, but often had complex changes, typically small regions of gain together with larger regions of loss. The boundaries of gains/losses tended to cluster, common sites being 54.5-55.5 Mb and 57.4-58.8 Mb. Overall, the peak frequency of loss (83% cancers) occurred at 61.9-62.9 Mb. We also found several 'minimal' regions of loss/gain. However, no mutations in candidate genes (TRADD, CDH5, CDH8 and CDH11) were detected. Cluster analysis based on copy number changes identified a large group of cancers that had lost most of 16q, and two smaller groups (one with few changes, one with a tendency to show copy number gain). Although all morphological types occurred in each cluster group, IDCs (especially GII/GIII) were relatively overrepresented in the smaller groups. Cluster groups were not independently associated with survival. Use of tiling-path aCGH prompted re-evaluation of the hypothetical pathways of breast carcinogenesis. ILCs have the simplest changes on 16q and probably diverge from the IDC lineage close to the stage of 16q loss. Higher-grade IDCs probably develop from low-grade lesions in most cases, but there remains evidence that some GII/GIII IDCs arise without a GI precursor.

Original publication

DOI

10.1038/sj.onc.1209659

Type

Journal article

Journal

Oncogene

Publication Date

19/10/2006

Volume

25

Pages

6544 - 6553

Keywords

Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Chromosome Aberrations, Chromosome Breakage, Chromosomes, Human, Pair 16, Cluster Analysis, DNA, Neoplasm, Gene Amplification, Gene Deletion, Genetic Linkage, Humans, Loss of Heterozygosity, Models, Statistical, Neoplasm Invasiveness, Neoplasm Staging, Nucleic Acid Hybridization, Tissue Array Analysis