Skip to main content

Advertisement

Log in

The manipulation of chromosomes by mankind: the uses of microcell-mediated chromosome transfer

  • Review
  • Published:
Chromosoma Aims and scope Submit manuscript

Abstract

Microcell-mediated chromosome transfer (MMCT) was a technique originally developed in the 1970s to transfer exogenous chromosome material into host cells. Although, the methodology has not changed considerably since this time it is being used to great success in progressing several different fields in modern day biology. MMCT is being employed by groups all over the world to hunt for tumour suppressor genes associated with specific cancers, DNA repair genes, senescence-inducing genes and telomerase suppression genes. Some of these genomic discoveries are being investigated as potential treatments for cancer. Other fields have taken advantage of MMCT, and these include assessing genomic stability, genomic imprinting, chromatin modification and structure and spatial genome organisation. MMCT has also been a very useful method in construction and manipulation of artificial chromosomes for potential gene therapies. Indeed, MMCT is used to transfer mainly fragmented mini-chromosome between cell types and into embryonic stem cells for the construction of transgenic animals. This review briefly discusses these various uses and some of the consequences and advancements made by different fields utilising MMCT technology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abeysinghe HR, Cao Q, Xu J, Pollock S, Veyberman Y, Guckert NL, Keng P, Wang N (2003) THY1 expression is associated with tumor suppression of human ovarian cancer. Cancer Genet Cytogenet 143:125–132

    Article  PubMed  CAS  Google Scholar 

  • Abeysinghe HR, Pollock SJ, Guckert NL, Veyberman Y, Keng P, Halterman M, Federoff HJ, Rosenblatt JP, Wang N (2004) The role of the THY1 gene in human ovarian cancer suppression based on transfection studies. Cancer Genet Cytogenet 149:1–10

    Article  PubMed  CAS  Google Scholar 

  • Acquati F, Morelli C, Cinquetti R, Bianchi MG, Porrini D, Varesco L, Gismondi V, Rocchetti R, Talevi S, Possati L, Magnanini C, Tibiletti MG, Bernasconi B, Daidone MG, Shridhar V, Smith DI, Negrini M, Barbanti-Brodano G, Taramelli R (2001) Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27. Oncogene 20:980–988

    Article  PubMed  CAS  Google Scholar 

  • Amor DJ, Bentley K, Ryan J, Perry J, Wong L, Slater H, Choo KHA (2004) Human centromere repositioning “in progress” Proc Natl Acad Sci U S A 101:6542–6547

    Article  PubMed  CAS  Google Scholar 

  • Anderson MJ, Stanbridge EJ (1993) Tumor suppressor genes studied by cell hybridization and chromosome transfer. FASEB J 7:826–833

    PubMed  CAS  Google Scholar 

  • Arima T, Drewell RA, Oshimura M, Wake N, Surani MA (2000) A novel imprinted gene, HYMAI, is located within an imprinted domain on human chromosome 6 containing ZAC. Genomics 67:248–255

    Article  PubMed  CAS  Google Scholar 

  • Athwal RS, Kaur GP (1996) Complementation mapping in microcell hybrids: localization of XRCC4 to 5q15–q21. Methods 9:12–19

    Article  PubMed  CAS  Google Scholar 

  • Auriche C, Carpani D, Conese M, Caci E, Zegarra-Moran O, Donini P, Ascenzioni F (2002) Functional human CFTR produced by a stable minichromosome. EMBO Rep 3:862–868

    Article  PubMed  CAS  Google Scholar 

  • Backsch C, Wagenbach N, Nonn M, Leistritz S, Stanbridge E, Schneider A, Durst M (2001) Microcell-mediated transfer of chromosome 4 into HeLa cells suppresses telomerase activity. Genes Chromosomes Cancer 31:196–198

    Article  PubMed  CAS  Google Scholar 

  • Bader SA, Fasching C, Brodeur GM, Stanbridge EJ (1991) Dissociation of suppression of tumorigenicity and differentiation in vitro effected by transfer of single human chromosomes into human neuroblastoma cells. Cell Growth Differ 2:245–255

    PubMed  CAS  Google Scholar 

  • Barrett JC (1994) Library of human chromosomes in mouse cells for mapping genes by function. Jpn J Cancer Res 85

  • Bayne RA, Broccoli D, Taggart MH, Thomson EJ, Farr CJ, Cooke HJ (1994) Sandwiching of a gene within 12 kb of a functional telomere and alpha satellite does not result in silencing. Hum Mol Genet 3:539–546

    PubMed  CAS  Google Scholar 

  • Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, Fauth C, Muller S, Eils R, Cremer C, Speicher MR, Cremer T (2005) Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol 3:e157

    Article  PubMed  CAS  Google Scholar 

  • Boyle S, Gilchrist S, Bridger JM, Mahy NL, Ellis JA, Bickmore WA (2001) The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. Hum Mol Genet 10:211–219

    PubMed  CAS  Google Scholar 

  • Bridger JM, Bickmore WA (1998) Putting the genome on the map. TIG 14:403–409

    PubMed  CAS  Google Scholar 

  • Bridger JM, Kill IR, Lichter P (1998) Association of pKi-67 with satellite DNA of the human genome in early G1 cells. Chromosome Res 6:13–24

    Article  PubMed  CAS  Google Scholar 

  • Bridger JM, Boyle S, Kill IR, Bickmore WA (2000) Re-modelling of nuclear architecture in quiescent and senescent human fibroblasts. Curr Biol 10:149–152

    Article  PubMed  CAS  Google Scholar 

  • Bridger JM, Sullivan BA, Bickmore WA, Sullivan G, McStay B, Grimes B (2001) Chromosome Res 9(supp 1):31

    Google Scholar 

  • Bryce SD, Forsyth NR, Fitzsimmons SA, Clark LJ, Bertram MJ, Cuthbert AP, Newbold RF, Pereira-Smith OM, Parkinson EK (1999) Genetic and functional analyses exclude mortality factor 4 (MORF4) as a keratinocyte senescence gene. Cancer Res 59:2038–2040

    PubMed  CAS  Google Scholar 

  • Cao Q, Abeysinghe H, Chow O, Xu J, Kaung H, Fong C, Keng P, Insel RA, Lee WM, Barrett JC, Wang N (2001) Suppression of tumorigenicity in human ovarian carcinoma cell line SKOV-3 by microcell-mediated transfer of chromosome 11. Cancer Genet Cytogenet 129:131–137

    Article  PubMed  CAS  Google Scholar 

  • Chen DJ, Park MS, Campbell E, Oshimura M, Liu P, Zhao Y, White BF, Siciliano MJ (1992) Assignment of a human DNA double-strand break repair gene (XRCC5) to chromosome 2. Genomics 13:1088–1094

    Article  PubMed  CAS  Google Scholar 

  • Cheng Y, Ko JM, Lung HL, Lo PH, Stanbridge EJ, Lung ML (2003) Monochromosome transfer provides functional evidence for growth-suppressive genes on chromosome 14 in nasopharyngeal carcinoma. Genes Chromosomes Cancer 37:359–368

    PubMed  CAS  Google Scholar 

  • Cheng Y, Lung HL, Wong PS, Hao da C, Man CS, Stanbridge EJ, Lung ML (2004) Chromosome 13q12 region critical for the viability and growth of nasopharyngeal carcinoma hybrids. Int J Cancer 109:357–362

    Article  PubMed  CAS  Google Scholar 

  • Coveler KJ, Yang SP, Sutton R, Milstein JM, Wu YQ, Bois KD, Beischel LS, Johnson JP, Shaffer LG (2002) A case of segmental paternal isodisomy of chromosome 14. Hum Genet 110:251–256

    Article  PubMed  CAS  Google Scholar 

  • Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2:292–301

    Article  PubMed  CAS  Google Scholar 

  • Cremer M, Hase J, Volm T, Brero A, Kreth G, Walter J, Fischer C, Solovei I, Cremer C, Cremer T (2001) Non-random radial higher-order chromatin arrangements in nuclei of diploid human cells. Chromosome Res 9:541–567

    Article  PubMed  CAS  Google Scholar 

  • Croft JA, Bridger JM, Boyle S, Perry P, Teague P, Bickmore WA (1999) Differences in the localization and morphology of chromosomes in the human nucleus. Cell Biol 145:1119–1131

    Article  PubMed  CAS  Google Scholar 

  • Cuthbert AP, Trott DA, Ekong RM, Jezzard S, England NL, Themis M, Todd CM, Newbold RF (1995) Construction and characterization of a highly stable human: rodent monochromosomal hybrid panel for genetic complementation and genome mapping studies. Cytogenet Cell Genet 71:68–76

    PubMed  CAS  Google Scholar 

  • Cuthbert AP, Bond J, Trott DA, Gill S, Broni J, Marriott A, Khoudoli G, Parkinson EK, Cooper CS, Newbold RF (1999) Telomerase repressor sequences on chromosome 3 and induction of permanent growth arrest in human breast cancer cells. J Natl Cancer Inst 91:37–45

    Article  PubMed  CAS  Google Scholar 

  • Darai E, Kost-Alimova M, Kiss H, Kansoul H, Klein G, Imreh S (2005) Evolutionarily plastic regions at human 3p21.3 coincide with tumor breakpoints identified by the “elimination test” Genomics (May 20 Epub)

  • Doherty AM, Fisher EM (2003) Microcell-mediated chromosome transfer (MMCT): small cells with huge potential. Mamm Genome 14:583–592

    Article  PubMed  Google Scholar 

  • Dong JT, Lamb PW, Rinker-Schaeffer CW, Vukanovic J, Ichikawa T, Isaacs JT, Barrett JC (1995) KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science 268:884–886

    PubMed  CAS  Google Scholar 

  • Dong JT, Suzuki H, Pin SS, Bova GS, Schalken JA, Isaacs WB, Barrett JC, Isaacs JT (1996) Down-regulation of the KAI1 metastasis suppressor gene during the progression of human prostatic cancer infrequently involves gene mutation or allelic loss. Cancer Res 56:4387–4390

    PubMed  CAS  Google Scholar 

  • Ebersole TA, Ross A, Clark E, McGill N, Schindelhauer D, Cooke H, Grimes B (2000) Mammalian artificial chromosome formation from circular alphoid input DNA does not require telomere repeats. Hum Mol Genet 9:1623–1631

    Article  PubMed  CAS  Google Scholar 

  • Ege T, Ringertz NR (1974) Preparation of microcells by enucleation of micronucleate cells. Exp Cell Res 87:378–382

    Article  PubMed  CAS  Google Scholar 

  • England NL, Cuthbert AP, Trott DA, Jezzard S, Nobori T, Carson DA, Newbold RF (1996) Identification of human tumour suppressor genes by monochromosome transfer: rapid growth-arrest response mapped to 9p21 is mediated solely by the cyclin-D-dependent kinase inhibitor gene, CDKN2A (p16INK4A). Carcinogenesis 17:1567–1575

    PubMed  CAS  Google Scholar 

  • Farr CJ, Bayne RA, Kipling D, Mills W, Critcher R, Cooke HJ (1995) Generation of a human X-derived minichromosome using telomere-associated chromosome fragmentation. EMBO J 14:5444–5454

    PubMed  CAS  Google Scholar 

  • Federico C, Saccone S, Andreozzi L, Motta S, Russo V, Carels N, Bernardi G (2004) The pig genome: compositional analysis and identification of the gene-richest regions in chromosomes and nuclei. Gene 343:245–251

    Article  PubMed  CAS  Google Scholar 

  • Flanagan JM, Healey S, Young J, Whitehall V, Trott DA, Newbold RF, Chenevix-Trench G (2004) Mapping of a candidate colorectal cancer tumor-suppressor gene to a 900-kilobase region on the short arm of chromosome 8. Genes Chromosomes Cancer 40:247–260

    Article  PubMed  CAS  Google Scholar 

  • Flejter WL, McDaniel LD, Askari M, Friedberg EC, Schultz RA (1992) Characterization of a complex chromosomal rearrangement maps the locus for in vitro complementation of xeroderma pigmentosum group D to human chromosome band 19q13. Genes Chromosomes Cancer 5:335–342

    PubMed  CAS  Google Scholar 

  • Fournier RE, Ruddle FH (1977) Microcell-mediated transfer of murine chromosomes into mouse, Chinese hamster, and human somatic cells. Proc Natl Acad Sci U S A 74:319–323

    PubMed  CAS  Google Scholar 

  • Friedberg EC, Henning K, Lambert C, Saxon PJ, Schultz RA, Sekhon GS, Stanbridge EJ (1990) Microcell-mediated chromosome transfer: a strategy for studying the genetics and molecular pathology of human hereditary diseases with abnormal responses to DNA damage. Basic Life Sci 52:257–267

    PubMed  CAS  Google Scholar 

  • Goodarzi G, Mashimo T, Watabe M, Cuthbert AP, Newbold RF, Pai SK, Hirota S, Hosobe S, Miura K, Bandyopadhyay S, Gross SC, Balaji KC, Watabe K (2001) Identification of tumor metastasis suppressor region on the short arm of human chromosome 20. Genes Chromosomes Cancer 32:33–42

    Article  PubMed  CAS  Google Scholar 

  • Grimes BR, Schindelhauer D, McGill NI, Ross A, Ebersole TA, Cooke HJ (2001) Stable gene expression from a mammalian artificial chromosome. EMBO Rep 2:910–914

    Article  PubMed  CAS  Google Scholar 

  • Grimes BR, Rhoades AA, Willard HF (2002) Alpha-satellite DNA and vector composition influence rates of human artificial chromosome formation. Molec Ther 5:798–805

    Article  CAS  Google Scholar 

  • Habermann FA, Cremer M, Walter J, Kreth G, Hase J, Bauer K, Wienberg J, Cremer T, Cremer C, Solovei I (2001) Arrangements of macro- and microchromosomes in chicken cells. Chromosome Res 9:569–584

    Article  PubMed  CAS  Google Scholar 

  • Hafezparast M, Kaur GP, Zdzienicka M, Athwal RS, Lehmann AR, Jeggo PA (1993) Subchromosomal localization of a gene (XRCC5) involved in double strand break repair to the region 2q34–36. Somat Cell Mol Genet 19:413–421

    Article  PubMed  CAS  Google Scholar 

  • Harrington JJ, Van Bokkelen G, Mays RW, Gustashaw K, Willard HF (1997) Formation of de novo centromeres and construction of first-generation human artificial microchromosomes. Nat Genet 15:345–355

    Article  PubMed  CAS  Google Scholar 

  • Henning KA, Novotny EA, Compton ST, Guan XY, Liu PP, Ashlock MA (1999) Human artificial chromosomes generated by modification of a yeast artificial chromosome containing both human alpha satellite and single-copy DNA sequences. Proc Natl Acad Sci U S A 96:592–597

    Article  PubMed  CAS  Google Scholar 

  • Hernandez D, Mee PJ, Martin JE, Tybulewicz VL, Fisher EM (1999) Transchromosomal mouse embryonic stem cell lines and chimeric mice that contain freely segregating segments of human chromosome 21. Hum Mol Genet 8:923–933

    Article  PubMed  CAS  Google Scholar 

  • Huertas D, Howe S, McGuigan A, Huxley C (2000) Expression of the human CFTR gene from episomal oriP-EBNA1-YACs in mouse cells. Hum Mol Genet 9:617–629

    Article  PubMed  CAS  Google Scholar 

  • Ikeno M, Grimes B, Okazaki T, Nakano M, Saitoh K, Hoshino H, McGill NI, Cooke H, Masumoto H (1998) Construction of YAC-based mammalian artificial chromosomes. Nat Biotechnol 16:431–439

    Article  PubMed  CAS  Google Scholar 

  • Ikeno M, Inagaki H, Nagata K, Morita M, Ichinose H, Okazaki T (2002) Generation of human artificial chromosomes expressing naturally controlled guanosine triphosphate cyclohydrolase I gene. Genes Cells 7:1021–1032

    Article  PubMed  CAS  Google Scholar 

  • Imreh S, Klein G, Zabarovsky ER (2003) Search for unknown tumor-antagonizing genes. Genes Chromosomes Cancer 38:307–321

    Article  PubMed  CAS  Google Scholar 

  • Inoue J, Mitsuya K, Maegawa S, Kugoh H, Kadota M, Okamura D, Shinohara T, Nishihara S, Takehara S, Yamauchi K, Schulz TC, Oshimura M (2001) Construction of 700 human/mouse A9 monochromosomal hybrids and analysis of imprinted genes on human chromosome 6. J Hum Genet 46:137–145

    Article  PubMed  CAS  Google Scholar 

  • Itzhaki JE, Barnett MA, MacCarthy AB, Buckle VJ, Brown WR, Porter AC (1992) Targeted breakage of a human chromosome mediated by cloned human telomeric DNA. Nat Genet 2:283–287

    Article  PubMed  CAS  Google Scholar 

  • Jeggo PA, Hafezparast M, Thompson AF, Broughton BC, Kaur GP, Zdzienicka MZ, Athwal RS (1992) Localization of a DNA repair gene (XRCC5) involved in double-strand-break rejoining to human chromosome 2. Proc Natl Acad Sci U S A 89:6423–6427

    PubMed  CAS  Google Scholar 

  • Julicher K, Marquitan G, Werner N, Bardenheuer W, Vieten L, Brocker F, Topal H, Seeber S, Opalka B, Schutte J (1999) Novel tumor suppressor locus in human chromosome region 3p14.2. J Natl Cancer Inst 91:1563–1568

    Article  PubMed  CAS  Google Scholar 

  • Kaur GP, Athwal RS (1989) Complementation of a DNA repair defect in xeroderma pigmentosum cells by transfer of human chromosome 9. Proc Natl Acad Sci U S A 86:8872–8876

    PubMed  CAS  Google Scholar 

  • Kaur GP, Athwal RS (1993) Complementation of DNA repair defect in xeroderma pigmentosum cells of group C by the transfer of human chromosome 5. Somat Cell Mol Genet 19:83–93

    Article  PubMed  CAS  Google Scholar 

  • Kazuki Y, Shinohara T, Tomizuka K, Katoh M, Ohguma A, Ishida I, Oshimura M (2001) Germline transmission of a transferred human chromosome 21 fragment in transchromosomal mice. J Hum Genet 46:600–603

    Article  PubMed  CAS  Google Scholar 

  • Kazuki Y, Kimura M, Nishigaki R, Kai Y, Abe S, Okita C, Shirayoshi Y, Schulz TC, Tomizuka K, Hanaoka K, Inoue T, Oshimura M (2004) Human chromosome 21q22.2-qter carries a gene(s) responsible for downregulation of mlc2a and PEBP in Down syndrome model mice. Biochem Biophys Res Commun 317:491–499

    Article  PubMed  CAS  Google Scholar 

  • Kelsell DP, Rooke L, Warne D, Bouzyk M, Cullin L, Cox S, West L, Povey S, Spurr NK (1995) Development of a panel of monochromosomal somatic cell hybrids for rapid gene mapping. Ann Hum Genet 59:233–241

    PubMed  CAS  Google Scholar 

  • Kholodnyuk ID, Kost-Alimova M, Yang Y, Kiss H, Fedorova L, Klein G, Imreh S (2002) The microcell hybrid-based “elimination test” identifies a 1-Mb putative tumor-suppressor region at 3p22.2–p22.1 centromeric to the homozygous deletion region detected in lung cancer. Genes Chromosomes Cancer 34:341–344

    Article  PubMed  CAS  Google Scholar 

  • Kirchgessner CU, Tosto LM, Biedermann KA, Kovacs M, Araujo D, Stanbridge EJ, Brown JM (1993) Complementation of the radiosensitive phenotype in severe combined immunodeficient mice by human chromosome 8. Cancer Res 53:6011–6016

    PubMed  CAS  Google Scholar 

  • Klein CB, Conway K, Wang XW, Bhamra RK, Lin XH, Cohen MD, Annab L, Barrett JC, Costa M (1991) Senescence of nickel-transformed cells by an X chromosome: possible epigenetic control. Science 251:796–799

    PubMed  CAS  Google Scholar 

  • Kodama S, Komatsu K, Okumura Y, Oshimura M (1992) Suppression of X-ray-induced chromosome aberrations in ataxia telangiectasia cells by introduction of a normal human chromosome 11. Mutat Res 293:31–37

    Google Scholar 

  • Koi M, Shimizu M, Morita H, Yamada H, Oshimura M (1989) Construction of mouse A9 clones containing a single human chromosome tagged with neomycin-resistance gene via microcell fusion. Jpn J Cancer Res 80:413–418

    PubMed  CAS  Google Scholar 

  • Kost-Alimova M, Fedorova L, Yang Y, Klein G, Imreh S (2004) Microcell-mediated chromosome transfer provides evidence that polysomy promotes structural instability in tumor cell chromosomes through asynchronous replication and breakage within late-replicating regions. Genes Chromosomes Cancer 40:316–324

    Google Scholar 

  • Kruzelock RP, Cuevas BD, Wiener JR, Xu FJ, Yu Y, Cabeza-Arvelaiz Y, Pershouse M, Lovell MM, Killary AM, Mills GB, Bast RC Jr (2000) Functional evidence for an ovarian cancer tumor suppressor gene on chromosome 22 by microcell-mediated chromosome transfer. Oncogene 19:6277–6285

    Google Scholar 

  • Kugoh H, Mitsuya K, Meguro M, Shigenami K, Schulz TC, Oshimura M (1999) Mouse A9 cells containing single human chromosomes for analysis of genomic imprinting. DNA Res 6:165–172

    Article  PubMed  CAS  Google Scholar 

  • Kugoh H, Fujiwara M, Kihara K, Fukui I, Horikawa I, Schulz TC, Oshimura M (2000) Cellular senescence of a human bladder carcinoma cell line (JTC-32) induced by a normal chromosome 11. Cancer Genet Cytogenet 116:158–163

    Article  PubMed  CAS  Google Scholar 

  • Kugoh H, Shigenami K, Funaki K, Barrett JC, Oshimura M (2003) Human chromosome 5 carries a putative telomerase repressor gene. Genes Chromosomes Cancer 36:37–47

    Article  PubMed  CAS  Google Scholar 

  • Kumata M, Shimizu M, Oshimura M, Uchida M, Tsutsui T (2002) Induction of cellular senescence in a telomerase negative human immortal fibroblast cell line, LCS-AF.1-3, by human chromosome 6. Int J Oncol 21:851–856

    PubMed  CAS  Google Scholar 

  • Kuroiwa Y, Shinohara T, Notsu T, Tomizuka K, Yoshida H, Takeda S, Oshimura M, Ishida I (1998) Efficient modification of a human chromosome by telomere-directed truncation in high homologous recombination-proficient chicken DT40 cells. Nucleic Acids Res 26:3447–3448

    Article  PubMed  CAS  Google Scholar 

  • Kuroiwa Y, Kasinathan P, Choi YJ, Naeem R, Tomizuka K, Sullivan EJ, Knott JG, Duteau A, Goldsby RA, Osborne BA, Ishida I, Robl JM (2002) Cloned transchromosomic calves producing human immunoglobulin. Nat Biotechnol 20:889–994

    Article  PubMed  CAS  Google Scholar 

  • Lambert C, Schultz RA, Smith M, Wagner-McPherson C, McDaniel LD, Donlon T, Stanbridge EJ, Friedberg EC (1991) Functional complementation of ataxia-telangiectasia group D (AT-D) cells by microcell-mediated chromosome transfer and mapping of the AT-D locus to the region 11q22–23. Proc Natl Acad Sci U S A 88:5907–5911

    PubMed  CAS  Google Scholar 

  • Lindenbaum M, Perkins E, Csonka E, Fleming E, Garcia L, Greene A, Gung L, Hadlaczky G, Lee E, Leung J, MacDonald N, Maxwell A, Mills K, Monteith D, Perez CF, Shellard J, Stewart S, Stodola T, Vandenborre D, Vanderbyl S, Ledebur HC Jr (2004) mammalian artificial chromosome engineering system (ACE System) applicable to biopharmaceutical protein production, transgenesis and gene-based cell therapy. Nucleic Acids Res 32:e172

    Article  PubMed  CAS  Google Scholar 

  • Lupton SD, Brunton LL, Kalberg VA, Overell RW (1991) Dominant positive and negative selection using a hygromycin phosphotransferase–thymidine kinase fusion gene. Mol Cell Biol 11:3374–3378

    PubMed  CAS  Google Scholar 

  • McDaniel LD, Schultz RA (1992) Elevated sister chromatid exchange phenotype of Bloom syndrome cells is complemented by human chromosome 15. Proc Natl Acad Sci U S A 89:7968–7972

    PubMed  CAS  Google Scholar 

  • Meaburn K, Cox H, Ellis J, Newbold R, Bridger J (2004) The role of the nuclear envelope in chromosome positioning: using monochromosome hybrid cells as a model system. Chromosome Res 12(supp 1):99

    Google Scholar 

  • Meguro M, Mitsuya K, Sui H, Shigenami K, Kugoh H, Nakao M, Oshimura M (1997) Evidence for uniparental, paternal expression of the human GABAA receptor subunit genes, using microcell-mediated chromosome transfer. Hum Mol Genet 6:2127–2133

    Article  PubMed  CAS  Google Scholar 

  • Mejia JE, Willmott A, Levy E, Earnshaw WC, Larin Z (2001) Functional complementation of a genetic deficiency with human artificial chromosomes. Am J Hum Genet 69:315–326

    Article  PubMed  CAS  Google Scholar 

  • Mills W, Critcher R, Lee C, Farr CJ (1999) Generation of an approximately 2.4 Mb human X centromere-based minichromosome by targeted telomere-associated chromosome fragmentation in DT40. Hum Mol Genet 8:751–761

    Article  PubMed  CAS  Google Scholar 

  • Mitsuya K, Meguro M, Lee MP, Katoh M, Schulz TC, Kugoh H, Yoshida MA, Niikawa N, Feinberg AP, Oshimura M (1999) LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids. Hum Mol Genet 8:1209–1217

    Article  PubMed  CAS  Google Scholar 

  • Miura N, Onuki N, Rathi A, Virmani A, Nakamoto S, Kishimoto Y, Murawaki Y, Kawasaki H, Hasegawa J, Oshimura M, Travis WD, Gazdar AF (2001) hTR repressor-related gene on human chromosome 10p15.1. Br J Cancer 85:1510–1514

    Article  PubMed  CAS  Google Scholar 

  • Morelli C, Sherratt T, Trabanelli C, Rimessi P, Gualandi F, Greaves MJ, Negrini M, Boyle JM, Barbanti-Brodano G (1997) Characterization of a 4-Mb region at chromosome 6q21 harboring a replicative senescence gene. Cancer Res 57:4153–4157

    PubMed  CAS  Google Scholar 

  • Nakabayashi K, Ogino H, Michishita E, Satoh N, Ayusawa D (1999) Introduction of chromosome 7 suppresses telomerase with shortening of telomeres in a human mesothelial cell line. Exp Cell Res 252:376–382

    Article  PubMed  CAS  Google Scholar 

  • Negrini M, Sabbioni S, Possati L, Rattan S, Corallini A, Barbanti-Brodano G, Croce CM (1994) Suppression of tumorigenicity of breast cancer cells by microcell-mediated chromosome transfer: studies on chromosomes 6 and 11. Cancer Res 54:1331–1336

    PubMed  CAS  Google Scholar 

  • Newbold RF (1997) Genetic control of telomerase and replicative senescence in human and rodent cells. Ciba Found Symp 211:177–189; discussion 189–197

    PubMed  CAS  Google Scholar 

  • Newbold RF (2002) The significance of telomerase activation and cellular immortalization in human cancer. Mutagenesis 17:539–550

    Article  PubMed  CAS  Google Scholar 

  • Nihei Y, Maruyama K, Endo Y, Sato T, Kobayashi K, Kaneko F (1996) Secretory component (polymeric immunoglobulin receptor) expression on human keratinocytes by stimulation with interferon-gamma and differences in response. J Dermatol Sci 11:214–222

    Article  PubMed  CAS  Google Scholar 

  • Nihei N, Kouprina N, Larionov V, Oshima J, Martin GM, Ichikawa T, Barrett JC (2002) Functional evidence for a metastasis suppressor gene for rat prostate cancer within a 60-kilobase region on human chromosome 8p21–p12. Cancer Res 62:367–370

    PubMed  CAS  Google Scholar 

  • Nishimoto A, Miura N, Horikawa I, Kugoh H, Murakami Y, Hirohashi S, Kawasaki H, Gazdar AF, Shay JW, Barrett JC, Oshimura M (2001) Functional evidence for a telomerase repressor gene on human chromosome 10p15.1. Oncogene 20:828–835

    Article  PubMed  CAS  Google Scholar 

  • Ohmura H, Tahara H, Suzuki M, Ide T, Shimizu M, Yoshida MA, Tahara E, Shay JW, Barrett JC, Oshimura M (1995) Restoration of the cellular senescence program and repression of telomerase by human chromosome 3. Jpn J Cancer Res 86:899–904

    PubMed  CAS  Google Scholar 

  • Okita C, Meguro M, Hoshiya H, Haruta M, Sakamoto YK, Oshimura M (2003) A new imprinted cluster on the human chromosome 7q21–q31, identified by human–mouse monochromosomal hybrids. Genomics 81:556–559

    Article  PubMed  CAS  Google Scholar 

  • Oshimura M, Kugoh HM, Shimizu M, Yamada H, Hashiba H, Horikawa I, Sasaki M (1989) Multiple chromosomes carrying tumor suppressor activity, via microcell-mediated chromosome transfer, for various tumor cell lines. Princess Takamatsu Symp 20:249–257

    PubMed  CAS  Google Scholar 

  • Parada LA, Misteli T (2002) Chromosome positioning in the interphase nucleus. Trends Cell Biol 12:425–432

    Article  PubMed  CAS  Google Scholar 

  • Parris CN (2004) Tumour suppressor genes in malignant melanoma. Chromosome Res 12:99

    Google Scholar 

  • Parris CN, Harris JD, Griffin DK, Cuthbert AP, Silver AJ, Newbold RF (1999) Functional evidence of novel tumor suppressor genes for cutaneous malignant melanoma. Cancer Res 59:516–520

    PubMed  CAS  Google Scholar 

  • Perez-Luz S, Huxley C (2004) Construction of episomal vectors carrying the intact human factor VIII gene for gene therapy. Chromosome Res 12(Supp 1):106

    Google Scholar 

  • Poignee M, Backsch C, Beer K, Jansen L, Wagenbach N, Stanbridge EJ, Kirchmayr R, Schneider A, Durst M (2001) Evidence for a putative senescence gene locus within the chromosomal region 10p14–p15. Cancer Res 61:7118–7121

    PubMed  CAS  Google Scholar 

  • Reddel RR (1998) Genes involved in the control of cellular proliferative potential. Ann NY Acad Sci 854:8–19

    PubMed  CAS  Google Scholar 

  • Ricketts SL, Garcia NF, Betz BL, Coleman WB (2002) Identification of candidate liver tumor suppressor genes from human 11p11.2–p12. Genes Chromosomes Cancer 33:47–59

    Article  PubMed  CAS  Google Scholar 

  • Rimessi P, Gualandi F, Morelli C, Trabanelli C, Wu Q, Possati L, Montesi M, Barrett JC, Barbanti-Brodano G (1994) Transfer of human chromosome 3 to an ovarian carcinoma cell line identifies three regions on 3p involved in ovarian cancer. Oncogene 9:3467–3474

    PubMed  CAS  Google Scholar 

  • Saffery R, Choo KH (2002) Strategies for engineering human chromosomes with therapeutic potential. J Gene Med 4:5–13

    Article  PubMed  Google Scholar 

  • Saffery R, Wong LH, Irvine DV, Bateman MA, Griffiths B, Cutts SM, Cancilla MR, Cendron AC, Stafford AJ, Choo KH (2001) Construction of neocentromere-based human minichromosomes by telomere-associated chromosomal truncation. Proc Natl Acad Sci U S A 98:5705–5710

    Article  PubMed  CAS  Google Scholar 

  • Sandhu AK, Hubbard K, Kaur GP, Jha KK, Ozer HL, Athwal RS (1994) Senescence of immortal human fibroblasts by the introduction of normal human chromosome 6. Proc Natl Acad Sci U S A 91:5498–5502

    PubMed  CAS  Google Scholar 

  • Saxon PJ, Srivatsan ES, Leipzig GV, Sameshima JH, Stanbridge EJ (1985) Selective transfer of individual human chromosomes to recipient cells. Mol Cell Biol 5:140–146

    PubMed  CAS  Google Scholar 

  • Saxon PJ, Srivatsan ES, Stanbridge EJ (1986) Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells. EMBO J 5:3461–3466

    PubMed  CAS  Google Scholar 

  • Schardin M, Cremer T, Hager HD, Lang M (1985) Specific staining of human chromosomes in Chinese hamster x man hybrid cell lines demonstrates interphase chromosome territories. Hum Genet 71:281–287

    Article  PubMed  CAS  Google Scholar 

  • Schindelhauer D, Laner A, Christan S, Cattani S, Ramalho A, Marques B, Beck S, Amaral M (2002) An engineered genomic CFTR-GFP fusion gene is expressed and correctly spliced on human artificial chromosomes. Eur J Hum Genet 10(Suppl. 1):301

    Google Scholar 

  • Schor SL, Johnson RT, Mullinger AM (1975) Perturbation of mammalian cell division. II. Studies on the isolation and characterization of human mini segregant cells. J Cell Sci 19:281–303

    PubMed  CAS  Google Scholar 

  • Schueler MG, Higgins AW, Rudd MK, Gustashaw K, Willard HF (2001) Genomic and genetic definition of a functional human centromere. Science 294:109–115

    Article  PubMed  CAS  Google Scholar 

  • Seitz S, Frege R, Jacobsen A, Weimer J, Arnold W, von Haefen C, Niederacher D, Schmutzler R, Arnold N, Scherneck S (2005) A network of clinically and functionally relevant genes is involved in the reversion of the tumorigenic phenotype of MDA-MB-231 breast cancer cells after transfer of human chromosome 8. Oncogene 24:869–879

    Article  PubMed  CAS  Google Scholar 

  • Sharp TV, Munoz F, Bourboulia D, Presneau N, Darai E, Wang HW, Cannon M, Butcher DN, Nicholson AG, Klein G, Imreh S, Boshoff C (2004) LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription. Proc Natl Acad Sci U S A 101:16531–16536

    Article  PubMed  CAS  Google Scholar 

  • Shinohara T, Tomizuka K, Miyabara S, Takehara S, Kazuki Y, Inoue J, Katoh M, Nakane H, Iino A, Ohguma A, Ikegami S, Inokuchi K, Ishida I, Reeves RH, Oshimura M (2001) Mice containing a human chromosome 21 model behavioral impairment and cardiac anomalies of Down's syndrome. Hum Mol Genet 10:1163–1175

    Article  PubMed  CAS  Google Scholar 

  • Speevak MD, Berube NG, McGowan-Jordan IJ, Bisson C, Lupton SD, Chevrette M (1995) Construction and analysis of microcell hybrids containing dual selectable tagged human chromosomes. Cytogenet Cell Genet 69:63–65

    PubMed  CAS  Google Scholar 

  • Stackhouse MA, Ortiz JB, Sato K, Chen DJ (1994) Functional complementation of the radiation-sensitive mutant M10 cell line by human chromosome 5. Mutat Res 323:47–52

    Article  PubMed  CAS  Google Scholar 

  • Stanbridge EJ (1992) Functional evidence for human tumour suppressor genes: chromosome and molecular genetic studies. Cancer Surv 12:5–24

    PubMed  CAS  Google Scholar 

  • Steenbergen RD, Kramer D, Meijer CJ, Walboomers JM, Trott DA, Cuthbert AP, Newbold RF, Overkamp WJ, Zdzienicka MZ, Snijders PJ (2001) Telomerase suppression by chromosome 6 in a human papillomavirus type 16-immortalized keratinocyte cell line and in a cervical cancer cell line. J Natl Cancer Inst 93:865–872

    Article  PubMed  CAS  Google Scholar 

  • Sullivan GJ, Bridger JM, Cuthbert AP, Newbold RF, Bickmore WA, McStay B (2001) Human acrocentric chromosomes with transcriptionally silent nuclear organizer regions associate with nucleoli. EMBO J 20:2867–2877

    Article  PubMed  CAS  Google Scholar 

  • Sun HB, Shen J, Yokota H (2000) Size-dependent positioning of human chromosomes in interphase nuclei. Biophys J 79:184–190

    PubMed  CAS  Google Scholar 

  • Szutorisz H, Lingner J, Cuthbert AP, Trott DA, Newbold RF, Nabholz M (2003) A chromosome 3-encoded repressor of the human telomerase reverse transcriptase (hTERT) gene controls the state of hTERT chromatin. Cancer Res 63:689–695

    PubMed  CAS  Google Scholar 

  • Tanabe H, Habermann FA, Solovei I, Cremer M, Cremer T (2002a) Non-random radial arrangements of interphase chromosome territories: evolutionary considerations and functional implications. Mutat Res 504:37–45

    PubMed  CAS  Google Scholar 

  • Tanabe H, Muller S, Neusser M, von Hase J, Calcagno E, Cremer M, Solovei I, Cremer C, Cremer T (2002b) Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Proc Natl Acad Sci U S A 99:4424–4429

    Article  PubMed  CAS  Google Scholar 

  • Tanabe H, Kupper K, Ishida T, Neusser M, Mizusawa H (2005) Inter- and intra-specific gene-density-correlated radial chromosome territory arrangements are conserved in Old World monkeys. Cytogenet Genome Res 108:255–261

    Article  PubMed  CAS  Google Scholar 

  • Tanaka H, Horikawa I, Kugoh H, Shimizu M, Barrett JC, Oshimura M (1999) Telomerase-independent senescence of human immortal cells induced by microcell-mediated chromosome transfer. Mol Carcinog 25:249–255

    Article  PubMed  CAS  Google Scholar 

  • Tanaka H, Horikawa I, Barrett JC, Oshimura M (2005) Evidence for inactivation of distinct telomerase repressor genes in different types of human cancers. Int J Cancer (in press)

  • Tindall KR, Glaab WE, Umar A, Risinger JI, Koi M, Barrett JC, Kunkel TA (1998) Complementation of mismatch repair gene defects by chromosome transfer. Mutat Res 402:15–22

    PubMed  CAS  Google Scholar 

  • Tomizuka K, Yoshida H, Uejima H, Kugoh H, Sato K, Ohguma A, Hayasaka M, Hanaoka K, Oshimura M, Ishida I (1997) Functional expression and germline transmission of a human chromosome fragment in chimaeric mice. Nat Genet 16:133–143

    Article  PubMed  CAS  Google Scholar 

  • Tomizuka K, Shinohara T, Yoshida H, Uejima H, Ohguma A, Tanaka S, Sato K, Oshimura M, Ishida I (2000) Double trans-chromosomic mice: maintenance of two individual human chromosome fragments containing Ig heavy and kappa loci and expression of fully human antibodies. Proc Natl Acad Sci U S A 97:722–727

    Article  PubMed  CAS  Google Scholar 

  • Uejima H, Mitsuya K, Kugoh H, Horikawa I, Oshimura M (1995) Normal human chromosome 2 induces cellular senescence in the human cervical carcinoma cell line SiHa. Genes Chromosomes Cancer 14:120–127

    PubMed  CAS  Google Scholar 

  • Upender MB, Habermann JK, McShane LM, Korn EL, Barrett JC, Difilippantonio MJ, Ried T (2004) Chromosome transfer induced aneuploidy results in complex dysregulation of the cellular transcriptome in immortalized and cancer cells. Cancer Res 64:6941–6949

    Article  PubMed  CAS  Google Scholar 

  • Vojta PJ, Futreal PA, Annab LA, Kato H, Pereira-Smith OM, Barrett JC (1996) Evidence for two senescence loci on human chromosome 1. Genes Chromosomes Cancer 16:55–63

    Article  PubMed  CAS  Google Scholar 

  • Wilding J, Meijne E, Haines J, Moody J, Edwards A, Newbold RF, Parris C, Cox R, Silver A (2002) Functional evidence from microcell-mediated chromosome transfer of myeloid leukemia suppressor genes on human chromosomes 7 and 11. Genes Chromosomes Cancer 34:390–397

    Article  PubMed  CAS  Google Scholar 

  • Wilson P, Cuthbert A, Marsh A, Arnold J, Flanagan J, Mulford C, Trott D, Baker E, Purdie D, Newbold R, Chenevix-Trench G (2003) Transfer of chromosome 8 into two breast cancer cell lines: total exclusion of three regions indicates location of putative in vitro growth suppressor genes. Cancer Genet Cytogenet 143:100–112

    Article  PubMed  CAS  Google Scholar 

  • Yamada H, Wake N, Fujimoto S, Barrett JC, Oshimura M (1990) Multiple chromosomes carrying tumor suppressor activity for a uterine endometrial carcinoma cell line identified by microcell-mediated chromosome transfer. Oncogene 5:1141–1147

    PubMed  CAS  Google Scholar 

  • Yang L, Leung AC, Ko JM, Lo PH, Tang JC, Srivastava G, Oshimura M, Stanbridge EJ, Daigo Y, Nakamura Y, Tang CM, Lau KW, Law S, Lung ML (2005) Tumor suppressive role of a 2.4 Mb 9q33–q34 critical region and DEC1 in esophageal squamous cell carcinoma. Oncogene 24:697–705

    Article  PubMed  CAS  Google Scholar 

  • Yoshida BA, Sokoloff MM, Welch DR, Rinker-Schaeffer CW (2000) Metastasis-suppressor genes: a review and perspective on an emerging field. J Natl Cancer Inst 92:1717–1730

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka H, Shirayoshi Y, Oshimura M (2001) A novel in vitro system for analyzing parental allele-specific histone acetylation in genomic imprinting. J Hum Genet 46:626–632

    Article  PubMed  CAS  Google Scholar 

  • Zdzienicka MZ, Jongmans W, Oshimura M, Priestley A, Whitmore GF, Jeggo PA (1995) Complementation analysis of the murine scid cell line. Radiat Res 143:238–244

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joanna M. Bridger.

Additional information

Communicated by D. Griffin

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meaburn, K.J., Parris, C.N. & Bridger, J.M. The manipulation of chromosomes by mankind: the uses of microcell-mediated chromosome transfer. Chromosoma 114, 263–274 (2005). https://doi.org/10.1007/s00412-005-0014-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00412-005-0014-8

Keywords

Navigation