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Vol. 89, No. 1-2, 2000
Issue release date: 2000
Section title: Paper
Cytogenet Cell Genet 89:121–128 (2000)
(DOI:10.1159/000015590)

DNA hypomethylation and unusual chromosome instability in cell lines fromICF syndrome patients

Tuck-Muller C.M. · Narayan A. · Tsien F. · Smeets D.F.C.M. · Sawyer J. · Fiala E.S. · Sohn O.S. · Ehrlich M.
aDepartment of Medical Genetics, University of South Alabama, Mobile, AL; bDepartment of Biochemistry, Tulane Cancer Center, and c Human Genetics Program, Tulane Medical School, New Orleans, LA (USA); dDepartment of Human Genetics, University Hospital Nijmegen (The Netherlands); eCytogenetics Lab, Children’s Hospital, Little Rock, AR; fDivision of Biochemical Pharmacology, American Health Foundation, Valhalla, NY (USA)

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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 6/26/2000
Issue release date: 2000

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 4

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: http://www.karger.com/CGR

Abstract

Abstract.

The ICF syndrome (&iumacr;mmunodeficiency, &cumacr;entromeric region instability, &fumacr;acial anomalies) is a unique DNA methylation deficiency disease diagnosed by an extraordinary collection of chromosomal anomalies specifically in the vicinity of the centromeres of chromosomes 1 and 16 (Chr1 and Chr16) in mitogen-stimulated lymphocytes. These aberrations include decondensation of centromere-adjacent (qh) heterochromatin, multiradial chromosomes with up to 12 arms, and whole-arm deletions. We demonstrate that lymphoblastoid cell lines from two ICF patients exhibit these Chr1 and Chr16 anomalies in 61% of the cells and continuously generate 1qh or 16qh breaks. No other consistent chromosomal abnormality was seen except for various telomeric associations, which had not been previously noted in ICF cells. Surprisingly, multiradials composed of arms of both Chr1 and Chr16 were favored over homologous associations and cells containing multiradials with 3 or >4 arms almost always displayed losses or gains of Chr1 or Chr16 arms from the metaphase. Our results suggest that decondensation of 1qh and 16qh often leads to unresolved Holliday junctions, chromosome breakage, arm missegregation, and the formation of multiradials that may yield more stable chromosomal abnormalities, such as translocations. These cell lines maintained the abnormal hypomethylation in 1qh and 16qh seen in ICF tissues. The ICF-specific hypomethylation occurs in only a small percentage of the genome, e.g., ICF brain DNA had 7% less 5-methylcytosine than normal brain DNA. The ICF lymphoblastoid cell lines, therefore, retain not only the ICF-specific pattern of chromosome rearrangements, but also of targeted DNA hypomethylation. This hypomethylation of heterochromatic DNA sequences is seen in many cancers and may predispose to chromosome rearrangements in cancer as well as in ICF.   


  

Author Contacts

Request reprints from Dr. Melanie Ehrlich, Human Genetics Program/SL31,Tulane Medical School, 1430 Tulane Avenue, New Orleans, LA 70112 (USA);telephone: 504-584-2449; fax: 504-584-1763;e-mail: ehrlich@mailhost.tcs.tulane.edu

  

Article Information

Supported in part by development funds from the Tulane Cancer Center and Grant CA81506 from the National Institutes of Health (to M.E.).

Received: Received 10 December 1999;
revision accepted 15 March 2000.
Number of Print Pages : 8
Number of Figures : 4, Number of Tables : 4, Number of References : 41

  

Publication Details

Cytogenetics and Cell Genetics
Founded 1962 as Cytogenetics by H.P. Klinger

Vol. 89, No. 1-2, Year 2000 (Cover Date: 2000)

Journal Editor: H.P. Klinger, Bronx, N.Y.; M. Schmid, Würzburg
ISSN: 0301–0171 (print), 1422–9816 (Online)

For additional information: http://www.karger.com/journals/ccg


Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 6/26/2000
Issue release date: 2000

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 4

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: http://www.karger.com/CGR


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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