Abstract
Terminal deletions are found frequently in both malignancies and clinically recognizable deletion syndromes in man. Little is known, particularly in cancer, of the specific mechanisms which lead to the generation of deleted chromosomes or the process by which these broken chromosomes are stabilized. We demonstrate that several examples of apparent terminal deletions are, in fact, subtelomeric translations which were not detectable using conventional cytogenetics. The unexpectedly high frequency of this phenomenon and the diversity of partner chromosomes involved in the subtelomeric translocations is consistent with a model in which telomere capture can stabilize chromosome breakage in man.
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References
Mitelman, F. Catalog of Chromosome Aberrations in Cancer (Wiley-Liss, New York, 1991).
Sandberg, A. The Chromosomes in Human Cancer and Leukemia (Elsevier, New York, 1990).
Trent, J. et al. Science 247, 568–571 (1990).
Bridges, C.B. Genetics 2, 445–465 (1917).
Bridges, C.B. Aberrations in chromosome materials. Scient. Pap. 2nd Int. Congr. Eugenics 1, 76 (1923).
Painter, T.S. & Muller, H.J. Parallel cytology and genetics of induced translocations and deletions in Drosophila. J. Hered. 20, 287–298 (1929).
McClintock, B. The production of homozygous deficient tissues with mutant characteristics by means of the aberrant behavior of ring-shaped chromosomes. Genetics 23, 315–376 (1938).
Meltzer, P.S., Guan, X.-Y., Burgess, A. & Trent, J.M. Rapid generation of region specific probes by chromosome microdissection and their application. Nature Genet. 1, 24–28 (1992).
Dowdy, S., Scanlon, D., Fashing, C., Casey, L. & Stanbridge, E. Irradiation microcell-mediated chromosome transfer (XMMCT): thegeneration of specific chromosomal arm deletions. Genes Chrom. Cancer 2, 318–327 (1990).
Meese, E. et al. Development and utilization of a somatic cell hybrid mapping panel to assign Not1 linking probes to the long arm of human chromosome 6. Genomics 12, 542–548 (1992).
McClintock, B. Cytological observations of deficiencies involving known genes, translocations and an inversion in Zea mays. Univ. Mo. Agric. Exp. Station Res. Bull. 163, 3–30 (1931).
Muller, H.J. The re-making of chromosomes. Collecting Net, Woods Hole 13, 181–195 and 198 (1938).
Haber, J.E. & Thorburn, P.C. Healing of broken linear dicentric chromosomes in yeast. Genetics 106, 207–226 (1984).
Blackburn, E.H. Structure and function of telomeres. Nature 350, 569–573 (1991).
Heim, S. & Mitelman, F. Cancer Cytogenetics (A. Liss, New York, 1987).
Altherr, M. et al. Molecular confirmation of Wolf-Hirschhorn syndrome with a subtle translocati n of chromosome 4. Am. J. hum. Genet. 49, 1235–1242 (1991).
Kuwano, A., Ledbetter, S.A., Dobyns, W.B., Emanuel, B.S., Ledbetter, D.H. Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization. Am. J. hum. Genet. 49, 707–714 (1991).
Ledbetter, D. Minireview: cryptic translocations and telomere integrity. Am. J. hum. Genet. 51, 451–456 (1992).
Blackburn, E.H. & Karrer, K.M. Genomic reorganization in ciliated protozoans. Am. Rev. Genet. 20, 501–521 (1986).
Kamper, J., Meinhardt, F., Gunge, N. & Esser, K. In vivo construction of linear vectors based on killer plasmids from Kluyveromyces lactis: selecton of a nuclear gene results in attachment of telomeres. Molec. cell. Biol. 9, 3931–3937, 1989.
Jager, D. & Philippsen, P. Stabilization of dicentric chromosomes in Saccharomyces cerevisiae by telomere addition to broken ends or by centromere deletion. EMBO J. 8, 247–254, 1989.
Wilkie, A.O.M., Lamb, J., Harris, P.C., Finney, R.D. & Higgs, D.R. A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n. Nature 346, 868–671 (1990).
Morin, G. Recognition of a chromosome truncation site associated with alpha-thalassaemia by human telomerase. Nature 353, 454–456 (1991).
Murane, J.P. & Yu, L.-C. Acquisition of telomere repreat sequences by transfected DNA integrated at the site of a chromosome break. Molec. cell. Biol. 13, 977–983, 1993.
de Lange, T., Shiue, L., Myers, R.M., Cox, D.R., Naylor, S.L., Killery, A.M. & Varmus, H.E. Structure and variability of human chromosome ends. Molec. cell Biol. 10, 518–527 (1990).
Pinkel, D., Landegent, J., Collins, C., Fuscoe, J., Segraves, R., Lucas, J. & Gray, J. Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc. natn. Acad. Sci. U.S.A. 85, 9138–9142 (1988).
Guan, X.-Y., Meltzer, P.S., Cao, J. & Trent, J.M. Rapid generation of region-specific genomic clones by chromosome microdissection: isolation of DNA from a region frequently deleted in malignant melanoma. Genomics 14, 680–684 (1992).
Telenius, H. et al. Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics 13, 718–725 (1992).
IJdo, J.W., Wells, R.A., Baldini, A. & Reeders, S.T. Improved telomere detection using a telomere repeat probe (TTAGGG)n generated by PCR. Nucleic Acid Res. 19, 19:4780 (1991).
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Meltzer, P., Guan, XY. & Trent, J. Telomere capture stabilizes chromosome breakage. Nat Genet 4, 252–255 (1993). https://doi.org/10.1038/ng0793-252
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DOI: https://doi.org/10.1038/ng0793-252