We aimed to directly align a chromosomal CGH (cCGH) pattern with the gene mapping data by taking advantage of the clustering of the GGCC motif at certain positions in the human genome. The alignment of chromosomal with sequence data was achieved by superimposition of (i) the fluorescence intensity of the sequence specific fluorochrome, Chromomycin A3 (CMA3), (ii) the cCGH fluorescence intensity profile of individual chromosomes and (iii) the GGCC density profile extracted from the Ensembl genome sequence database. The superimposition of these three pieces of information allowed us to precisely localize regions of amplification in the neuroblastoma cell line STA-NB-15. Two prominent cCGH peaks were noted, one at 2p24.3, the position 15.4 mega base (Mb), and the other at 2p23.2, 29.51 Mb. FISH and high resolution array CGH (aCGH) experiments disclosed an amplification of MYCN (16 Mb) and ALK (29.2–29.9 Mb), thus confirming the cCGH data. The combined visualization of sequence information and cCGH data drastically improves the resolution of the method to less than 2 Mb.

Ambrosini A, Paul S, Hu S, Riethman H: Human subtelomeric duplicon structure and organization. Genome Biol 8:R151 (2007).
Aviv A, Levy D, Mangel M: Growth, telomere dynamics and successful and unsuccessful human aging. Mech Ageing Dev 124:829–837 (2003).
Bentz M, Plesch A, Stilgenbauer S, Dohner H, Lichter P: Minimal sizes of deletions detected by comparative genomic hybridization. Genes Chromosomes Cancer 21:172–175 (1998).
Chen QR, Bilke S, Wei JS, Whiteford CC, Cenacchi N, et al: cDNA array-CGH profiling identifies genomic alterations specific to stage and MYCN-amplification in neuroblastoma. BMC Genomics 5:70 (2004).
Chen QR, Bilke S, Khan J: High-resolution cDNA microarray-based comparative genomic hybridization analysis in neuroblastoma. Cancer Lett 228:71–81 (2005).
de Lange T, Shiue L, Myers RM, Cox DR, Naylor SL, Killery AM, Varmus HE: Structure and variability of human chromosome ends. Mol Cell Biol 10:518–527 (1990).
Garnis C, Buys TP, Lam WL: Genetic alteration and gene expression modulation during cancer progression. Mol Cancer 3:9 (2004).
Hou MH, Robinson H, Gao YG, Wang AH: Crystal structure of the [Mg2+-(chromomycin A3)2]-d(TTGGCCAA)2 complex reveals GGCC binding specificity of the drug dimer chelated by a metal ion. Nucleic Acids Res 32:2214–2222 (2004).
Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, et al: Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821 (1992).
Kallioniemi A, Kallioniemi OP, Piper J, Tanner M, Stokke T, et al: Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc Natl Acad Sci USA 91:2156–2160 (1994).
Kallioniemi OP, Kallioniemi A, Sudar D, Rutovitz D, Gray JW, et al: Comparative genomic hybridization: a rapid new method for detecting and mapping DNA amplification in tumors. Semin Cancer Biol 4:41–46 (1993).
Kallioniemi OP, Kallioniemi A, Piper J, Isola J, Waldman FM, et al: Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors. Genes Chromosomes Cancer 10:231–243 (1994).
Kirchhoff M, Gerdes T, Rose H, Maahr J, Ottesen AM, Lundsteen C: Detection of chromosomal gains and losses in comparative genomic hybridization analysis based on standard reference intervals. Cytometry 31:163–173 (1998).
Kirchhoff M, Gerdes T, Maahr J, Rose H, Bentz M, et al: Deletions below 10 megabasepairs are detected in comparative genomic hybridization by standard reference intervals. Genes Chromosomes Cancer 25:410–413 (1999).
Kirchhoff M, Rose H, Lundsteen C: High resolution comparative genomic hybridisation in clinical cytogenetics. J Med Genet 38:740–744 (2001).
Knight SJ, Flint J: Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis. J Med Genet 37:401–409 (2000).
Kowalska A, Bozsaky E, Ramsauer T, Rieder D, Bindea G, et al: A new platform linking chromosomal and sequence information. Chromosome Res 15:327–339 (2007).
Lichter P, Bentz M, Joos S: Detection of chromosomal aberrations by means of molecular cytogenetics: painting of chromosomes and chromosomal subregions and comparative genomic hybridization. Methods Enzymol 254:334–359 (1995).
Lichter P, Joos S, Bentz M, Lampel S: Comparative genomic hybridization: uses and limitations. Semin Hematol 37:348–357 (2000).
Lin KW, Yan J: The telomere length dynamic and methods of its assessment. J Cell Mol Med 9:977–989 (2005).
Narath R, Ambros IM, Kowalska A, Bozsaky E, Boukamp P, Ambros PF: Induction of senescence in MYCN amplified neuroblastoma cell lines by hydroxyurea. Genes Chromosomes Cancer 46:130–142 (2007).
Pinkel D, Segraves R, Sudar D, Clark S, Poole I, et al: High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 20:207–211 (1998).
Piper J, Rutovitz D, Sudar D, Kallioniemi A, Kallioniemi OP, et al: Computer image analysis of comparative genomic hybridization. Cytometry 19:10–26 (1995).
Riethman H, Ambrosini A, Paul S: Human subtelomere structure and variation. Chromosome Res 13:505–515 (2005).
Schweizer D: Reverse fluorescent chromosome banding with chromomycin and DAPI. Chromosoma 58:307–324 (1976).
Schweizer D: Counterstain-enhanced chromosome banding. Hum Genet 57:1–14 (1981).
Schweizer D, Ambros PF: Chromosome banding. Stain combinations for specific regions. Methods Mol Biol 29:97–112 (1994).
Selzer RR, Richmond TA, Pofahl NJ, Green RD, Eis PS, et al: Analysis of chromosome breakpoints in neuroblastoma at sub-kilobase resolution using fine-tiling oligonucleotide array CGH. Genes Chromosomes Cancer 44:305–319 (2005).
Stock C, Kager L, Fink FM, Gadner H, Ambros PF: Chromosomal regions involved in the pathogenesis of osteosarcomas. Genes Chromosomes Cancer 28:329–336 (2000).
Wang N: Methodologies in cancer cytogenetics and molecular cytogenetics. Am J Med Genet 115:118–124 (2002).
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