Array painting reveals a high frequency of balanced translocations in breast cancer cell lines that break in cancer-relevant genes.
Chromosome translocations in the common epithelial cancers are abundant, yet little is known about them. They have been thought to be almost all unbalanced and therefore dismissed as mostly mediating tumour suppressor loss. We present a comprehensive analysis by array painting of the chromosome translocations of breast cancer cell lines HCC1806, HCC1187 and ZR-75-30. In array painting, chromosomes are isolated by flow cytometry, amplified and hybridized to DNA microarrays. A total of 200 breakpoints were identified and all were mapped to 1 Mb resolution on bacterial artificial chromosome (BAC) arrays, then 40 selected breakpoints, including all balanced breakpoints, were further mapped on tiling-path BAC arrays or to around 2 kb resolution using oligonucleotide arrays. Many more of the translocations were balanced at 1 Mb resolution than expected, either reciprocal (eight in total) or balanced for at least one participating chromosome (19 paired breakpoints). Second, many of the breakpoints were at genes that are plausible targets of oncogenic translocation, including balanced breaks at CTCF, EP300/p300 and FOXP4. Two gene fusions were demonstrated, TAX1BP1-AHCY and RIF1-PKD1L1. Our results support the idea that chromosome rearrangements may play an important role in common epithelial cancers such as breast cancer.
Howarth
K D
KD
Department of Pathology, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, UK.
Blood
K A
KA
Ng
B L
BL
Beavis
J C
JC
Chua
Y
Y
Cooke
S L
SL
Raby
S
S
Ichimura
K
K
Collins
V P
VP
Carter
N P
NP
Edwards
P A W
PA
D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D019457:Chromosome Breakage; D002874:Chromosome Mapping / Q000379:methods; D020223:Chromosome Painting / Q000379:methods*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D052138:Genes, Neoplasm; D015894:Genome, Human; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics; D009857:Oncogenes / Q000502:physiology; D034501:Telomere-Binding Proteins / Q000235:genetics; D046888:Tissue Array Analysis / Q000379:methods*; D014178:Translocation, Genetic
D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; C455507:PKD1L1 protein, human; C529679:RIF1-PKD1L1 protein, human; C492743:Rif1 protein, human; D034501:Telomere-Binding Proteins