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. 1999 Dec;81(8):1328–1334. doi: 10.1038/sj.bjc.6695007

Molecular cytogenetic analysis of 11 new breast cancer cell lines

F Forozan 1, R Veldman 1, C A Ammerman 2, N Z Parsa 1, A Kallioniemi 1, O-P Kallioniemi 1, S P Ethier 2
PMCID: PMC2362964  PMID: 10604729

Abstract

We describe a survey of genetic changes by comparative genomic hybridization (CGH) in 11 human breast cancer cell lines recently established in our laboratory. The most common gains took place at 8q (73%), 1q (64%), 7q (64%), 3q (45%) and 7p (45%), whereas losses were most frequent at Xp (54%), 8p (45%), 18q (45%) and Xq (45%). Many of the cell lines displayed prominent, localized DNA amplifications by CGH. One-third of these loci affected breast cancer oncogenes, whose amplifications were validated with specific probes: 17q12 (two cell lines with ERBB2 amplifications), 11q13 (two with cyclin-D1), 8p11–p12 (two with FGFR1) and 10q25 (one with FGFR2). Gains and amplifications affecting 8q were the most common genetic alterations in these cell lines with the minimal, common region of involvement at 8q22–q23. No high-level MYC (at 8q24) amplifications were found in any of the cell lines. Two-thirds of the amplification sites took place at loci not associated with established oncogenes, such as 1q41–q43, 7q21–q22, 7q31, 8q23, 9p21–p23, 11p12–p14, 15q12–q14, 16q13–q21, 17q23, 20p11–p12 and 20q13. Several of these locations have not been previously reported and may harbour important genes whose amplification is selected for during cancer development. In summary, this set of breast cancer cell lines displaying prominent DNA amplifications should facilitate discovery and functional analysis of genes and signal transduction pathways contributing to breast cancer development. © 1999 Cancer Research Campaign

Keywords: molecular cytogenetics, FISH, CGH, chromosomal aberrations, oncogene amplification

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Selected References

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  1. Adnane J., Gaudray P., Dionne C. A., Crumley G., Jaye M., Schlessinger J., Jeanteur P., Birnbaum D., Theillet C. BEK and FLG, two receptors to members of the FGF family, are amplified in subsets of human breast cancers. Oncogene. 1991 Apr;6(4):659–663. [PubMed] [Google Scholar]
  2. Anzick S. L., Kononen J., Walker R. L., Azorsa D. O., Tanner M. M., Guan X. Y., Sauter G., Kallioniemi O. P., Trent J. M., Meltzer P. S. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science. 1997 Aug 15;277(5328):965–968. doi: 10.1126/science.277.5328.965. [DOI] [PubMed] [Google Scholar]
  3. Bischoff J. R., Anderson L., Zhu Y., Mossie K., Ng L., Souza B., Schryver B., Flanagan P., Clairvoyant F., Ginther C. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. 1998 Jun 1;17(11):3052–3065. doi: 10.1093/emboj/17.11.3052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Collins C., Rommens J. M., Kowbel D., Godfrey T., Tanner M., Hwang S. I., Polikoff D., Nonet G., Cochran J., Myambo K. Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8703–8708. doi: 10.1073/pnas.95.15.8703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Devilee P., Cornelisse C. J. Somatic genetic changes in human breast cancer. Biochim Biophys Acta. 1994 Dec 30;1198(2-3):113–130. doi: 10.1016/0304-419x(94)90009-4. [DOI] [PubMed] [Google Scholar]
  6. Ethier S. P. Human breast cancer cell lines as models of growth regulation and disease progression. J Mammary Gland Biol Neoplasia. 1996 Jan;1(1):111–121. doi: 10.1007/BF02096306. [DOI] [PubMed] [Google Scholar]
  7. Ethier S. P., Mahacek M. L., Gullick W. J., Frank T. S., Weber B. L. Differential isolation of normal luminal mammary epithelial cells and breast cancer cells from primary and metastatic sites using selective media. Cancer Res. 1993 Feb 1;53(3):627–635. [PubMed] [Google Scholar]
  8. Ethier S. P., Summerfelt R. M., Cundiff K. C., Asch B. B. The influence of growth factors on the proliferative potential of normal and primary breast cancer-derived human breast epithelial cells. Breast Cancer Res Treat. 1991 Jan-Feb;17(3):221–230. doi: 10.1007/BF01806371. [DOI] [PubMed] [Google Scholar]
  9. Fischer U., Müller H. W., Sattler H. P., Feiden K., Zang K. D., Meese E. Amplification of the MET gene in glioma. Genes Chromosomes Cancer. 1995 Jan;12(1):63–65. doi: 10.1002/gcc.2870120111. [DOI] [PubMed] [Google Scholar]
  10. Forozan F., Karhu R., Kononen J., Kallioniemi A., Kallioniemi O. P. Genome screening by comparative genomic hybridization. Trends Genet. 1997 Oct;13(10):405–409. doi: 10.1016/s0168-9525(97)01244-4. [DOI] [PubMed] [Google Scholar]
  11. Garcia R., Yu C. L., Hudnall A., Catlett R., Nelson K. L., Smithgall T., Fujita D. J., Ethier S. P., Jove R. Constitutive activation of Stat3 in fibroblasts transformed by diverse oncoproteins and in breast carcinoma cells. Cell Growth Differ. 1997 Dec;8(12):1267–1276. [PubMed] [Google Scholar]
  12. Geradts J., Wilson P. A. High frequency of aberrant p16(INK4A) expression in human breast cancer. Am J Pathol. 1996 Jul;149(1):15–20. [PMC free article] [PubMed] [Google Scholar]
  13. Guan X. Y., Meltzer P. S., Dalton W. S., Trent J. M. Identification of cryptic sites of DNA sequence amplification in human breast cancer by chromosome microdissection. Nat Genet. 1994 Oct;8(2):155–161. doi: 10.1038/ng1094-155. [DOI] [PubMed] [Google Scholar]
  14. Houldsworth J., Cordon-Cardo C., Ladanyi M., Kelsen D. P., Chaganti R. S. Gene amplification in gastric and esophageal adenocarcinomas. Cancer Res. 1990 Oct 1;50(19):6417–6422. [PubMed] [Google Scholar]
  15. Kallioniemi A., Kallioniemi O. P., Piper J., Tanner M., Stokke T., Chen L., Smith H. S., Pinkel D., Gray J. W., Waldman F. M. Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2156–2160. doi: 10.1073/pnas.91.6.2156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Karhu R., Kähkönen M., Kuukasjärvi T., Pennanen S., Tirkkonen M., Kallioniemi O. Quality control of CGH: impact of metaphase chromosomes and the dynamic range of hybridization. Cytometry. 1997 Jul 1;28(3):198–205. doi: 10.1002/(sici)1097-0320(19970701)28:3<198::aid-cyto3>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  17. Kononen J., Bubendorf L., Kallioniemi A., Bärlund M., Schraml P., Leighton S., Torhorst J., Mihatsch M. J., Sauter G., Kallioniemi O. P. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998 Jul;4(7):844–847. doi: 10.1038/nm0798-844. [DOI] [PubMed] [Google Scholar]
  18. Kuukasjärvi T., Karhu R., Tanner M., Kähkönen M., Schäffer A., Nupponen N., Pennanen S., Kallioniemi A., Kallioniemi O. P., Isola J. Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. Cancer Res. 1997 Apr 15;57(8):1597–1604. [PubMed] [Google Scholar]
  19. Mahacek M. L., Beer D. G., Frank T. S., Ethier S. P. Finite proliferative lifespan in vitro of a human breast cancer cell strain isolated from a metastatic lymph node. Breast Cancer Res Treat. 1993 Dec;28(3):267–276. doi: 10.1007/BF00666588. [DOI] [PubMed] [Google Scholar]
  20. Ram T. G., Dilts C. A., Dziubinski M. L., Pierce L. J., Ethier S. P. Insulin-like growth factor and epidermal growth factor independence in human mammary carcinoma cells with c-erbB-2 gene amplification and progressively elevated levels of tyrosine-phosphorylated p185erbB-2. Mol Carcinog. 1996 Mar;15(3):227–238. doi: 10.1002/(SICI)1098-2744(199603)15:3<227::AID-MC8>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  21. Ram T. G., Kokeny K. E., Dilts C. A., Ethier S. P. Mitogenic activity of neu differentiation factor/heregulin mimics that of epidermal growth factor and insulin-like growth factor-I in human mammary epithelial cells. J Cell Physiol. 1995 Jun;163(3):589–596. doi: 10.1002/jcp.1041630320. [DOI] [PubMed] [Google Scholar]
  22. Ried T., Just K. E., Holtgreve-Grez H., du Manoir S., Speicher M. R., Schröck E., Latham C., Blegen H., Zetterberg A., Cremer T. Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast tumors reveals different patterns of chromosomal gains and losses in fibroadenomas and diploid and aneuploid carcinomas. Cancer Res. 1995 Nov 15;55(22):5415–5423. [PubMed] [Google Scholar]
  23. Sartor C. I., Dziubinski M. L., Yu C. L., Jove R., Ethier S. P. Role of epidermal growth factor receptor and STAT-3 activation in autonomous proliferation of SUM-102PT human breast cancer cells. Cancer Res. 1997 Mar 1;57(5):978–987. [PubMed] [Google Scholar]
  24. Sen S., Zhou H., White R. A. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene. 1997 May 8;14(18):2195–2200. doi: 10.1038/sj.onc.1201065. [DOI] [PubMed] [Google Scholar]
  25. Tanner M. M., Tirkkonen M., Kallioniemi A., Isola J., Kuukasjärvi T., Collins C., Kowbel D., Guan X. Y., Trent J., Gray J. W. Independent amplification and frequent co-amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer. Cancer Res. 1996 Aug 1;56(15):3441–3445. [PubMed] [Google Scholar]
  26. Tirkkonen M., Tanner M., Karhu R., Kallioniemi A., Isola J., Kallioniemi O. P. Molecular cytogenetics of primary breast cancer by CGH. Genes Chromosomes Cancer. 1998 Mar;21(3):177–184. [PubMed] [Google Scholar]
  27. Wullich B., Müller H. W., Fischer U., Zang K. D., Meese E. Amplified met gene linked to double minutes in human glioblastoma. Eur J Cancer. 1993;29A(14):1991–1995. doi: 10.1016/0959-8049(93)90460-w. [DOI] [PubMed] [Google Scholar]

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