title: A comprehensive study of chromosome 16q in invasive ductal and lobular breast carcinoma using array CGH.
abstract: 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.
authors.affiliation: Molecular and Population Genetics Laboratory, Cancer Research UK, Lincoln's Inn Fields, London, UK. rebecca.roylance@cancer.org.uk
authors.forename: R
authors.initials: R
authors.lastname: Roylance
authors.forename: P
authors.initials: P
authors.lastname: Gorman
authors.forename: T
authors.initials: T
authors.lastname: Papior
authors.forename: Y-L
authors.initials: YL
authors.lastname: Wan
authors.forename: M
authors.initials: M
authors.lastname: Ives
authors.forename: J E
authors.initials: JE
authors.lastname: Watson
authors.forename: C
authors.initials: C
authors.lastname: Collins
authors.forename: N
authors.initials: N
authors.lastname: Wortham
authors.forename: C
authors.initials: C
authors.lastname: Langford
authors.forename: H
authors.initials: H
authors.lastname: Fiegler
authors.forename: N
authors.initials: N
authors.lastname: Carter
authors.forename: C
authors.initials: C
authors.lastname: Gillett
authors.forename: P
authors.initials: P
authors.lastname: Sasieni
authors.forename: S
authors.initials: S
authors.lastname: Pinder
authors.forename: A
authors.initials: A
authors.lastname: Hanby
authors.forename: I
authors.initials: I
authors.lastname: Tomlinson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000235:genetics*; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002885:Chromosomes, Human, Pair 16; D016000:Cluster Analysis; D004273:DNA, Neoplasm; D005784:Gene Amplification; D017353:Gene Deletion; D008040:Genetic Linkage; D006801:Humans; D019656:Loss of Heterozygosity; D015233:Models, Statistical; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization / Q000379:methods*; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D004273:DNA, Neoplasm