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.
Breast cancer Cell lines aCGH
This is a preview of subscription content, log in to check access.
We thank Breakthrough Breast Cancer and Cancer Research UK for their continued support of this work.
Stamps AC, Davies SC, Burman J et al (1994) Analysis of proviral integration in human mammary epithelial cell lines immortalized by retroviral infection with a temperature-sensitive SV40 T-antigen construct. Int J Cancer 57:865–874. doi:10.1002/ijc.2910570616CrossRefPubMedGoogle Scholar
Clarke C, Titley J, Davies S et al (1994) An immunomagnetic separation method using superparamagnetic (MACS) beads for large-scale purification of human mammary luminal and myoepithelial cells. Epithelial Cell Biol 3:38–46PubMedGoogle Scholar
Reis-Filho JS, Simpson PT, Jones C et al (2005) Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity. J Pathol 207:1–13. doi:10.1002/path.1806CrossRefPubMedGoogle Scholar
Jonsson G, Staaf J, Olsson E et al (2007) High-resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization. Genes Chromosomes Cancer 46:543–558. doi:10.1002/gcc.20438CrossRefPubMedGoogle Scholar
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-06-1371CrossRefPubMedGoogle Scholar
Savage K, Leung S, Todd SK et al (2008) Distribution and significance of caveolin 2 expression in normal breast and invasive breast cancer: an immunofluorescence and immunohistochemical analysis. Breast Cancer Res Treat 110:245–256. doi:10.1007/s10549-007-9718-1CrossRefPubMedGoogle Scholar
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
Seitz S, Wassmuth P, Plaschke J et al (2003) Identification of microsatellite instability and mismatch repair gene mutations in breast cancer cell lines. Genes Chromosomes Cancer 37:29–35. doi:10.1002/gcc.10196CrossRefPubMedGoogle Scholar
Schlegel J, Stumm G, Scherthan H et al (1995) Comparative genomic in situ hybridization of colon carcinomas with replication error. Cancer Res 55:6002–6005PubMedGoogle Scholar
Bergamaschi A, Kim YH, Wang P et al (2006) Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosomes Cancer 45:1033–1040. doi:10.1002/gcc.20366CrossRefPubMedGoogle Scholar
Lai PS, Cheah PY, Kadam P et al (2006) Overexpression of RB1 transcript is significantly correlated with 13q14 allelic imbalance in colorectal carcinomas. Int J Cancer 119:1061–1066. doi:10.1002/ijc.21945CrossRefPubMedGoogle Scholar
Campbell PJ, Stephens PJ, Pleasance ED et al (2008) Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat Genet 40:722–729. doi:10.1038/ng.128CrossRefPubMedGoogle Scholar