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Breast Cancer Research
Published in: Breast Cancer Research 1/2006

Open Access 01-02-2006 | Research article

Comprehensive copy number profiles of breast cancer cell model genomes

Authors: Ashleen Shadeo, Wan L Lam

Published in: Breast Cancer Research | Issue 1/2006

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Abstract

Introduction

Breast cancer is the most commonly diagnosed cancer in women worldwide and consequently has been extensively investigated in terms of histopathology, immunochemistry and familial history. Advances in genome-wide approaches have contributed to molecular classification with respect to genomic changes and their subsequent effects on gene expression. Cell lines have provided a renewable resource that is readily used as model systems for breast cancer cell biology. A thorough characterization of their genomes to identify regions of segmental DNA loss (potential tumor-suppressor-containing loci) and gain (potential oncogenic loci) would greatly facilitate the interpretation of biological data derived from such cells. In this study we characterized the genomes of seven of the most commonly used breast cancer model cell lines at unprecedented resolution using a newly developed whole-genome tiling path genomic DNA array.

Methods

Breast cancer model cell lines MCF-7, BT-474, MDA-MB-231, T47D, SK-BR-3, UACC-893 and ZR-75-30 were investigated for genomic alterations with the submegabase-resolution tiling array (SMRT) array comparative genomic hybridization (CGH) platform. SMRT array CGH provides tiling coverage of the human genome permitting break-point detection at about 80 kilobases resolution. Two novel discrete alterations identified by array CGH were verified by fluorescence in situ hybridization.

Results

Whole-genome tiling path array CGH analysis identified novel high-level alterations and fine-mapped previously reported regions yielding candidate genes. In brief, 75 high-level gains and 48 losses were observed and their respective boundaries were documented. Complex alterations involving multiple levels of change were observed on chromosome arms 1p, 8q, 9p, 11q, 15q, 17q and 20q. Furthermore, alignment of whole-genome profiles enabled simultaneous assessment of copy number status of multiple components of the same biological pathway. Investigation of about 60 loci containing genes associated with the epidermal growth factor family (epidermal growth factor receptor, HER2, HER3 and HER4) revealed that all seven cell lines harbor copy number changes to multiple genes in these pathways.

Conclusion

The intrinsic genetic differences between these cell lines will influence their biologic and pharmacologic response as an experimental model. Knowledge of segmental changes in these genomes deduced from our study will facilitate the interpretation of biological data derived from such cells.
Appendix
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Literature
1.
Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55: 74-108.CrossRefPubMed
2.
Bray F, McCarron P, Parkin DM: The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res. 2004, 6: 229-239. 10.1186/bcr932.CrossRefPubMedPubMedCentral
3.
Simpson PT, Reis-Filho JS, Gale T, Lakhani SR: Molecular evolution of breast cancer. J Pathol. 2005, 205: 248-254. 10.1002/path.1691.CrossRefPubMed
4.
Hanahan D, Weinberg RA: The hallmarks of cancer. Cell. 2000, 100: 57-70. 10.1016/S0092-8674(00)81683-9.CrossRefPubMed
5.
6.
Kallioniemi OP, Kallioniemi A, Kurisu W, Thor A, Chen LC, Smith HS, Waldman FM, Pinkel D, Gray JW: ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. Proc Natl Acad Sci USA. 1992, 89: 5321-5325.CrossRefPubMedPubMedCentral
7.
Shimada M, Imura J, Kozaki T, Fujimori T, Asakawa S, Shimizu N, Kawaguchi R: Detection of Her2/neu, c-MYC and ZNF217 gene amplification during breast cancer progression using fluorescence in situ hybridization. Oncol Rep. 2005, 13: 633-641.PubMed
8.
Jarvinen TA, Tanner M, Rantanen V, Barlund M, Borg A, Grenman S, Isola J: Amplification and deletion of topoisomerase IIalpha associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer. Am J Pathol. 2000, 156: 839-847.CrossRefPubMedPubMedCentral
9.
Lacroix M, Leclercq G: Relevance of breast cancer cell lines as models for breast tumours: an update. Breast Cancer Res Treat. 2004, 83: 249-289. 10.1023/B:BREA.0000014042.54925.cc.CrossRefPubMed
10.
Emens LA, Davidson NE: Trastuzumab in breast cancer. Oncology (Williston Park). 2004, 18: 1117-1128.
11.
Baselga J: Herceptin alone or in combination with chemotherapy in the treatment of HER2-positive metastatic breast cancer: pivotal trials. Oncology. 2001, 61 (Suppl 2): 14-21. 10.1159/000055397.CrossRefPubMed
12.
Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, et al: First-line Herceptin monotherapy in metastatic breast cancer. Oncology. 2001, 61 (Suppl 2): 37-42. 10.1159/000055400.CrossRefPubMed
13.
Kallioniemi A, Kallioniemi OP, Piper J, Tanner M, Stokke T, Chen L, Smith HS, Pinkel D, Gray JW, Waldman FM: Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc Natl Acad Sci USA. 1994, 91: 2156-2160.CrossRefPubMedPubMedCentral
14.
Kytola S, Rummukainen J, Nordgren A, Karhu R, Farnebo F, Isola J, Larsson C: Chromosomal alterations in 15 breast cancer cell lines by comparative genomic hybridization and spectral karyotyping. Genes Chromosomes Cancer. 2000, 28: 308-317. 10.1002/1098-2264(200007)28:3<308::AID-GCC9>3.0.CO;2-B.CrossRefPubMed
15.
Forozan F, Mahlamaki EH, Monni O, Chen Y, Veldman R, Jiang Y, Gooden GC, Ethier SP, Kallioniemi A, Kallioniemi OP: Comparative genomic hybridization analysis of 38 breast cancer cell lines: a basis for interpreting complementary DNA microarray data. Cancer Res. 2000, 60: 4519-4525.PubMed
16.
Davies JJ, Wilson IM, Lam WL: Array CGH technologies and their applications to cancer genomes. Chromosome Res. 2005, 13: 237-248. 10.1007/s10577-005-2168-x.CrossRefPubMed
17.
Pinkel D, Albertson DG: Array comparative genomic hybridization and its applications in cancer. Nat Genet. 2005, 37 (Suppl): S11-17. 10.1038/ng1569.CrossRefPubMed
18.
Collins C, Volik S, Kowbel D, Ginzinger D, Ylstra B, Cloutier T, Hawkins T, Predki P, Martin C, Wernick M, et al: Comprehensive genome sequence analysis of a breast cancer amplicon. Genome Res. 2001, 11: 1034-1042. 10.1101/gr.GR1743R.CrossRefPubMedPubMedCentral
19.
Albertson DG, Ylstra B, Segraves R, Collins C, Dairkee SH, Kowbel D, Kuo WL, Gray JW, Pinkel D: Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat Genet. 2000, 25: 144-146. 10.1038/75985.CrossRefPubMed
20.
Hodgson JG, Chin K, Collins C, Gray JW: Genome amplification of chromosome 20 in breast cancer. Breast Cancer Res Treat. 2003, 78: 337-345. 10.1023/A:1023085825042.CrossRefPubMed
21.
Orsetti B, Nugoli M, Cervera N, Lasorsa L, Chuchana P, Ursule L, Nguyen C, Redon R, du Manoir S, Rodriguez C, et al: Genomic and expression profiling of chromosome 17 in breast cancer reveals complex patterns of alterations and novel candidate genes. Cancer Res. 2004, 64: 6453-6460. 10.1158/0008-5472.CAN-04-0756.CrossRefPubMed
22.
Albertson DG: Profiling breast cancer by array CGH. Breast Cancer Res Treat. 2003, 78: 289-298. 10.1023/A:1023025506386.CrossRefPubMed
23.
Nessling M, Richter K, Schwaenen C, Roerig P, Wrobel G, Wessendorf S, Fritz B, Bentz M, Sinn HP, Radlwimmer B, et al: Candidate genes in breast cancer revealed by microarray-based comparative genomic hybridization of archived tissue. Cancer Res. 2005, 65: 439-447.PubMed
24.
Kauraniemi P, Barlund M, Monni O, Kallioniemi A: New amplified and highly expressed genes discovered in the ERBB2 amplicon in breast cancer by cDNA microarrays. Cancer Res. 2001, 61: 8235-8240.PubMed
25.
Monni O, Barlund M, Mousses S, Kononen J, Sauter G, Heiskanen M, Paavola P, Avela K, Chen Y, Bittner ML, et al: Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer. Proc Natl Acad Sci USA. 2001, 98: 5711-5716. 10.1073/pnas.091582298.CrossRefPubMedPubMedCentral
26.
Hyman E, Kauraniemi P, Hautaniemi S, Wolf M, Mousses S, Rozenblum E, Ringner M, Sauter G, Monni O, Elkahloun A, et al: Impact of DNA amplification on gene expression patterns in breast cancer. Cancer Res. 2002, 62: 6240-6245.PubMed
27.
Clark J, Edwards S, John M, Flohr P, Gordon T, Maillard K, Giddings I, Brown C, Bagherzadeh A, Campbell C, et al: Identification of amplified and expressed genes in breast cancer by comparative hybridization onto microarrays of randomly selected cDNA clones. Genes Chromosomes Cancer. 2002, 34: 104-114. 10.1002/gcc.10039.CrossRefPubMed
28.
Pollack JR, Sorlie T, Perou CM, Rees CA, Jeffrey SS, Lonning PE, Tibshirani R, Botstein D, Borresen-Dale AL, Brown PO: Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proc Natl Acad Sci USA. 2002, 99: 12963-12968. 10.1073/pnas.162471999.CrossRefPubMedPubMedCentral
29.
Ishkanian AS, Malloff CA, Watson SK, DeLeeuw RJ, Chi B, Coe BP, Snijders A, Albertson DG, Pinkel D, Marra MA, et al: A tiling resolution DNA microarray with complete coverage of the human genome. Nat Genet. 2004, 36: 299-303. 10.1038/ng1307.CrossRefPubMed
30.
de Leeuw RJ, Davies JJ, Rosenwald A, Bebb G, Gascoyne RD, Dyer MJ, Staudt LM, Martinez-Climent JA, Lam WL: Comprehensive whole genome array CGH profiling of mantle cell lymphoma model genomes. Hum Mol Genet. 2004, 13: 1827-1837. 10.1093/hmg/ddh195.CrossRefPubMed
31.
Watson SK, deLeeuw RJ, Ishkanian AS, Malloff CA, Lam WL: Methods for high throughput validation of amplified fragment pools of BAC DNA for constructing high resolution CGH arrays. BMC Genomics. 2004, 5: 6-10.1186/1471-2164-5-6.CrossRefPubMedPubMedCentral
32.
Chi B, DeLeeuw RJ, Coe BP, MacAulay C, Lam WL: SeeGH – a software tool for visualization of whole genome array comparative genomic hybridization data. BMC Bioinformatics. 2004, 5: 13-10.1186/1471-2105-5-13.CrossRefPubMedPubMedCentral
33.
34.
Jong K, Marchiori E, Meijer G, Vaart AV, Ylstra B: Breakpoint identification and smoothing of array comparative genomic hybridization data. Bioinformatics. 2004, 20: 3636-3637.CrossRefPubMed
35.
36.
Henderson LJ, Lestou VS, Ludkovski O, Robichaud M, Chhanabhai M, Gascoyne RD, Klasa RJ, Connors JM, Marra MA, Horsman DE, et al: Delineation of a minimal region of deletion at 6q16.3 in follicular lymphoma and construction of a bacterial artificial chromosome contig spanning a 6-megabase region of 6q16-q21. Genes Chromosomes Cancer. 2004, 40: 60-65. 10.1002/gcc.20013.CrossRefPubMed
37.
Savinainen KJ, Linja MJ, Saramaki OR, Tammela TL, Chang GT, Brinkmann AO, Visakorpi T: Expression and copy number analysis of TRPS1, EIF3S3 and MYC genes in breast and prostate cancer. Br J Cancer. 2004, 90: 1041-1046. 10.1038/sj.bjc.6601648.CrossRefPubMedPubMedCentral
38.
Rummukainen J, Kytola S, Karhu R, Farnebo F, Larsson C, Isola JJ: Aberrations of chromosome 8 in 16 breast cancer cell lines by comparative genomic hybridization, fluorescence in situ hybridization, and spectral karyotyping. Cancer Genet Cytogenet. 2001, 126: 1-7. 10.1016/S0165-4608(00)00387-3.CrossRefPubMed
39.
Zhao X, Li C, Paez JG, Chin K, Janne PA, Chen TH, Girard L, Minna J, Christiani D, Leo C, et al: An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays. Cancer Res. 2004, 64: 3060-3071. 10.1158/0008-5472.CAN-03-3308.CrossRefPubMed
40.
Maass N, Rosel F, Schem C, Hitomi J, Jonat W, Nagasaki K: Amplification of the BCAS2 gene at chromosome 1p13.3-21 in human primary breast cancer. Cancer Lett. 2002, 185: 219-223. 10.1016/S0304-3835(02)00286-0.CrossRefPubMed
41.
Qi C, Zhu YT, Chang J, Yeldandi AV, Rao MS, Zhu YJ: Potentiation of estrogen receptor transcriptional activity by breast cancer amplified sequence 2. Biochem Biophys Res Commun. 2005, 328: 393-398. 10.1016/j.bbrc.2004.12.187.CrossRefPubMed
42.
Nagasaki K, Maass N, Manabe T, Hanzawa H, Tsukada T, Kikuchi K, Yamaguchi K: Identification of a novel gene, DAM1, amplified at chromosome 1p13.3-21 region in human breast cancer cell lines. Cancer Lett. 1999, 140 (1–2): 219-226. 10.1016/S0304-3835(99)00091-9.CrossRefPubMed
43.
Lapuk A, Volik S, Vincent R, Chin K, Kuo WL, de Jong P, Collins C, Gray JW: Computational BAC clone contig assembly for comprehensive genome analysis. Genes Chromosomes Cancer. 2004, 40: 66-71. 10.1002/gcc.20016.CrossRefPubMed
44.
Falck J, Coates J, Jackson SP: Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature. 2005, 434: 605-611. 10.1038/nature03442.CrossRefPubMed
45.
Jaquemar D, Schenker T, Trueb B: An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts. J Biol Chem. 1999, 274: 7325-7333. 10.1074/jbc.274.11.7325.CrossRefPubMed
46.
Dantzig AH, Hoskins JA, Tabas LB, Bright S, Shepard RL, Jenkins IL, Duckworth DC, Sportsman JR, Mackensen D, Rosteck PR, et al: Association of intestinal peptide transport with a protein related to the cadherin superfamily. Science. 1994, 264: 430-433.CrossRefPubMed
47.
Ma Y, Pannicke U, Schwarz K, Lieber MR: Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell. 2002, 108: 781-794. 10.1016/S0092-8674(02)00671-2.CrossRefPubMed
48.
Fletcher GC, Patel S, Tyson K, Adam PJ, Schenker M, Loader JA, Daviet L, Legrain P, Parekh R, Harris AL, et al: hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan. Br J Cancer. 2003, 88: 579-585. 10.1038/sj.bjc.6600740.CrossRefPubMedPubMedCentral
49.
Snijders AM, Nowak N, Segraves R, Blackwood S, Brown N, Conroy J, Hamilton G, Hindle AK, Huey B, Kimura K, et al: Assembly of microarrays for genome-wide measurement of DNA copy number. Nat Genet. 2001, 29: 263-264. 10.1038/ng754.CrossRefPubMed
50.
Xie D, Jauch A, Miller CW, Bartram CR, Koeffler HP: Discovery of over-expressed genes and genetic alterations in breast cancer cells using a combination of suppression subtractive hybridization, multiplex FISH and comparative genomic hybridization. Int J Oncol. 2002, 21: 499-507.PubMed
51.
Watson MB, Bahia H, Ashman JN, Berrieman HK, Drew P, Lind MJ, Greenman J, Cawkwell L: Chromosomal alterations in breast cancer revealed by multicolour fluorescence in situ hybridization. Int J Oncol. 2004, 25: 277-283.PubMed
52.
Barlund M, Tirkkonen M, Forozan F, Tanner MM, Kallioniemi O, Kallioniemi A: Increased copy number at 17q22-q24 by CGH in breast cancer is due to high-level amplification of two separate regions. Genes Chromosomes Cancer. 1997, 20: 372-376. 10.1002/(SICI)1098-2264(199712)20:4<372::AID-GCC8>3.0.CO;2-Z.CrossRefPubMed
53.
Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J: The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992, 70: 431-442. 10.1016/0092-8674(92)90167-B.CrossRefPubMed
54.
Wu GJ, Sinclair CS, Paape J, Ingle JN, Roche PC, James CD, Couch FJ: 17q23 amplifications in breast cancer involve the PAT1, RAD51C, PS6K, and SIGma1B genes. Cancer Res. 2000, 60: 5371-5375.PubMed
55.
Bhargava R, Gerald WL, Li AR, Pan Q, Lal P, Ladanyi M, Chen B: EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. Mod Pathol. 2005, 18: 1027-1033. 10.1038/modpathol.3800438.CrossRefPubMed
56.
Oda K, Matsuoka Y, Funahashi A, Kitano H: A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol. 2005, 1: msb4100014-E1-msb4100014-E17. 10.1038/msb4100014.CrossRef
57.
Graus-Porta D, Beerli RR, Daly JM, Hynes NE: ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J. 1997, 16: 1647-1655. 10.1093/emboj/16.7.1647.CrossRefPubMedPubMedCentral
Metadata
Title
Comprehensive copy number profiles of breast cancer cell model genomes
Authors
Ashleen Shadeo
Wan L Lam
Publication date
01-02-2006
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2006
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1370

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