A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines
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Tumour cell lines derived from breast cancer patients constitute one of the cornerstones of breast cancer research. To characterise breast cancer cell lines at the genetic level, we have developed a full tiling path bacterial artificial chromosome (BAC) array collection for comparative genomic hybridisation (aCGH). This aCGH BAC collection covers 98% of the entire human genome at a resolution of 40–60 kbp. We have used this platform alongside an in-house produced 17 K cDNA microarray set to characterise the genetic and transcriptomic profiles of 24 breast cancer cell lines, as well as cell types derived from non-diseased breast. We demonstrate that breast cancer cell lines have genomic and transcriptomic features that recapitulate those of primary breast cancers and can be reliably subclassified into basal-like and luminal subgroups. By overlaying aCGH and transcriptomic data, we have identified 753 genes whose expression correlate with copy number; this list comprised numerous oncogenes recurrently amplified and overexpressed in breast cancer (e.g., HER2, MYC, CCND1 and AURKA). Finally, we demonstrate that although breast cancer cell lines have genomic features usually found in grade III breast cancers (i.e., gains of 1q, 8q and 20q), basal-like and luminal cell lines are characterised by distinct genomic aberrations.
KeywordsBreast cancer Cell lines aCGH
We thank Breakthrough Breast Cancer and Cancer Research UK for their continued support of this work.
- 13.Freshney RI (2005) Culture of animal cells: a manual of basic technique, 5th edn. Wiley-Liss, New YorkGoogle Scholar
- 25.Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc [Ser A] 57:289–300Google Scholar
- 28.Savage K, Lambros MB, Robertson D et al (2007) Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis. Clin Cancer Res 13:90–101. doi:10.1158/1078-0432.CCR-06-1371 CrossRefPubMedGoogle Scholar
- 31.Natrajan R, Lambros MB, Rodrigues Pinilla SM, et al (2008) Tiling path genomic profiling of grade III invasive ductal breast cancers. Clin Cancer Res (in press)Google Scholar
- 53.Konig A, Happle R, Bornholdt D et al (2000) Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome. Am J Med Genet 90:339–346. doi:10.1002/(SICI)1096-8628(20000214)90:4<339::AID-AJMG15>3.0.CO;2-5 CrossRefPubMedGoogle Scholar