Summary
A proportion of breast cancers acquire genetic alterations at 17q11.2–q12 (HER-2/neu), 20q13.2 (ZNF217 gene) and 17p13.1 (p53). We describe a unique technique (Comet–FISH) in which we documented relative genetic instability at p53 and HER-2/neu gene loci within a panel of malignant breast cancer cell lines (MCF-7; MDA-MB-468 and CRL-2336). Furthermore, Comet–FISH data were consistent with preferential repair of the p53 locus following gentoxic insult and suggest that this assay may be quite useful for the study of genetic instability.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
JC Keen NE Davidson (2003) ArticleTitleThe biology of breast carcinoma Cancer 97 825–833 Occurrence Handle10.1002/cncr.11126 Occurrence Handle12548582
M Berwick P Vineis (2000) ArticleTitleMarkers of DNA repair and susceptibility to cancer in humans: an epidemiologic review J Natl Cancer Inst 92 874–897 Occurrence Handle10.1093/jnci/92.11.874 Occurrence Handle1:CAS:528:DC%2BD3cXksF2qtbY%3D Occurrence Handle10841823
MR Spitz TC Hsu (1994) ArticleTitleMutagen sensitivity as a marker of cancer risk Cancer Detect Prev 18 299–303 Occurrence Handle1:STN:280:ByqD2szisVE%3D Occurrence Handle7526974
DP Cahill KW Kinzler B Vogelstein C Lengauer (1999) ArticleTitleGenetic instability and darwinian selection in tumours Trends Cell Biol 9 M57–M60 Occurrence Handle10.1016/S0962-8924(99)01661-X Occurrence Handle1:CAS:528:DC%2BD3cXnt1ClsA%3D%3D Occurrence Handle10611684
SN Powell LA Kachnic (2003) ArticleTitleRoles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation Oncogene 22 5784–5791 Occurrence Handle10.1038/sj.onc.1206678 Occurrence Handle1:CAS:528:DC%2BD3sXmslemt7s%3D Occurrence Handle12947386
AR Venkitaraman (2002) ArticleTitleCancer susceptibility and the functions of BRCA1 and BRCA2 Cell 108 171–182 Occurrence Handle10.1016/S0092-8674(02)00615-3 Occurrence Handle1:CAS:528:DC%2BD38XhtV2hsLc%3D Occurrence Handle11832208
JS Ross JA Fletcher GP Linette J Stec E Clark M Ayers WF Symmans L Pusztai KJ Bloom (2003) ArticleTitleThe HER-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy Oncologist 8 307–325 Occurrence Handle10.1634/theoncologist.8-4-307 Occurrence Handle1:CAS:528:DC%2BD3sXmvFSqt74%3D Occurrence Handle12897328
JE Eyfjord S Thorlacius M Steinarsdottir R Valgardsdottir HM Ogmundsdottir K Anamthawat-Jonsson (1995) ArticleTitlep53 abnormalities and genomic instability in primary human breast carcinomas Cancer Res 55 646–651 Occurrence Handle1:STN:280:ByqC3snisVA%3D Occurrence Handle7530599
M Gasco IG Yulug T Crook (2003) ArticleTitleTP53 mutations in familial breast cancer: functional aspects Hum Mutat 21 301–306 Occurrence Handle10.1002/humu.10173 Occurrence Handle1:CAS:528:DC%2BD3sXis1yjtLo%3D Occurrence Handle12619116
P Yaswen MR Stampfer (2002) ArticleTitleMolecular changes accompanying senescence and immortalization of cultured human mammary epithelial cells Int J Biochem Cell Biol 34 1382–1394 Occurrence Handle10.1016/S1357-2725(02)00047-X Occurrence Handle1:CAS:528:DC%2BD38XmsVersbg%3D Occurrence Handle12200033
JS Winston J Ramanaryanan E Levine (2004) ArticleTitleHER-2/neu evaluation in breast cancer are we there yet Am J Clin Pathol 121 IssueIDSuppl S33–S49 Occurrence Handle15298149
RG Bristow Q Hu A Jang S Chung J Peacock S Benchimol R Hill (1998) ArticleTitleRadioresistant MTp53-expressing rat embryo cell transformants exhibit increased DNA-dsb rejoining during exposure to ionizing radiation Oncogene 16 1789–1802 Occurrence Handle10.1038/sj.onc.1201935 Occurrence Handle1:CAS:528:DyaK1cXivVWkurY%3D Occurrence Handle9583677
PL Olive (2002) ArticleTitleThe comet assay An overview of techniques. Methods Mol Biol 203 179–194 Occurrence Handle1:CAS:528:DC%2BD38XksVWjur4%3D
RR Tice E Agurell D Anderson B Burlinson A Hartmann H Kobayashi Y Miyamae E Rojas JC Ryu YF Sasaki (2000) ArticleTitlecell gel/comet assay: guidelines for in vitro and in’vivo’genetic toxicology testing Environ Mol Mutagen 35 206–221 Occurrence Handle10.1002/(SICI)1098-2280(2000)35:3<206::AID-EM8>3.0.CO;2-J Occurrence Handle1:CAS:528:DC%2BD3cXis1Wrurg%3D Occurrence Handle10737956
TS Kumaravel K Tanaka M Arif K Ohshima A Ohgami M Takeshita M Kikuchi N Kamada (1997) ArticleTitleClonal identification of trisomies 3,5 and X in angioimmunoblastic lymphadenopathy with dysproteinemia by fluorescence in situ hybridization Leuk Lymphoma 24 523–532 Occurrence Handle1:STN:280:ByiB2c7gtVI%3D Occurrence Handle9086442
JL Fernandez F Vazquez-Gundin MT Rivero A Genesca J Gosalvez V Goyanes (2001) ArticleTitleDBD-fish on neutral comets: simultaneous analysis of DNA single- and double-strand breaks in individual cells Exp Cell Res 270 102–109 Occurrence Handle10.1006/excr.2001.5328 Occurrence Handle1:CAS:528:DC%2BD3MXnsVKrtr8%3D Occurrence Handle11597132
DJ McKenna NF Rajab SR McKeown G McKerr VJ McKelvey-Martin (2003) ArticleTitleUse of the Comet–FISH assay to demonstrate repair of the TP53 gene region in two human bladder carcinoma cell lines Radiat Res 159 49–56 Occurrence Handle1:CAS:528:DC%2BD3sXjslyqsQ%3D%3D Occurrence Handle12492368
TM Runger M Kotas M Poot M Leverkus B Epe PA Jeggo D Hellfritsch (2003) ArticleTitleReduced joining of DNA ends correlates with chromosomal instability in three melanoma cell lines Tumour Biol 24 100–108 Occurrence Handle10.1159/000071083 Occurrence Handle12853705
CL Limoli E Giedzinski WF Morgan SG Swarts GD Jones W Hyun (2003) ArticleTitlePersistent oxidative stress in chromosomally unstable cells Cancer Res 63 3107–3111 Occurrence Handle1:CAS:528:DC%2BD3sXks1eitb0%3D Occurrence Handle12810636
A Schaeferhenrich G Beyer-Sehlmeyer G Festag A Kuechler N Haag A Weise T Liehr U Claussen B Marian W Sendt J Scheele BL Pool-Zobel (2003) ArticleTitleHuman adenoma cells are highly susceptible to the genotoxic action of 4-hydroxy-2-nonenal Mutat Res 526 19–32 Occurrence Handle1:CAS:528:DC%2BD3sXjtFWru7w%3D Occurrence Handle12714179
A Rapp C Bock H Dittmar KO Greulich (2000) ArticleTitleUV-A breakage sensitivity of human chromosomes as measured by Comet–FISH depends on gene density and not on the chromosome size J Photochem Photobiol B 56 109–117 Occurrence Handle10.1016/S1011-1344(00)00052-X Occurrence Handle1:CAS:528:DC%2BD3cXmsFyrurc%3D Occurrence Handle11079471
K Trenz A Rothfuss P Schutz G Speit (2002) ArticleTitleMutagen sensitivity of peripheral blood from women carrying a BRCA1 or BRCA2 mutation Mutat Res 500 89–96 Occurrence Handle1:CAS:528:DC%2BD38XhvVWltr8%3D Occurrence Handle11890937
S Colleu-Durel N Guitton K Nourgalieva F Legue J Leveque B Danic C Chenal (2004) ArticleTitleAlkaline single-cell gel electrophoresis (Comet assay): a simple technique to show genomic instability in sporadic breast cancer Eur J Cancer 40 445–451 Occurrence Handle10.1016/j.ejca.2003.09.033 Occurrence Handle1:CAS:528:DC%2BD2cXmvFGjsQ%3D%3D Occurrence Handle14746864
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kumaravel, T.S., Bristow, R.G. Detection of genetic instability at HER-2/neu and p53 loci in breast cancer cells sing Comet–FISH. Breast Cancer Res Treat 91, 89–94 (2005). https://doi.org/10.1007/s10549-004-5780-0
Issue Date:
DOI: https://doi.org/10.1007/s10549-004-5780-0