Increased Rate of Spontaneous Mitotic Recombination in T Lymphocytes from a Bloom's Syndrome Patient Using a Flow-cytometric Assay at HLA-A Locus

Overview

Journal Jpn J Cancer Res

Specialty Oncology

Date 1994 Jun 1

PMID 8063614

Citations 5

Authors

Y Kusunoki

T Hayashi

Y Hirai

J Kushiro

K Tatsumi

T Kurihara

M Zghal

M R Kamoun

H Takebe

A Jeffreys

Affiliations

Soon will be listed here.

Abstract

Bloom's syndrome (BS) is an autosomal recessive disorder conferring high propensity for cancer and displaying a high degree of genetic instability; the frequency of sister chromatid exchange is characteristically 10 times above background. The symmetrical four-armed chromatid interchanges are much more readily detected in peripheral blood lymphocytes of BS patients, suggesting that the frequency of somatic recombination is also increased. In the present study, the rate of spontaneous loss of HLA-A allele expression was estimated following fluctuation analysis in cultured T lymphocytes using a flow-cytometric assay. It was found to be 10 times or more higher than normal in lymphocytes from a BS patient. Molecular and chromosome analyses showed that all 13 independent variants from the patient were most likely derived from somatic recombinations. Further tests for loss of heterozygosity at a closely linked proximal locus, HLA-DQA1, showed that as many as half of the recombinants retained heterozygosity irrespective of the donor. The results suggest that the HLA region is hyperrecombinogenic in somatic cells and that the elevated recombination rate in BS cells results from the general increase at ordinary sites and not from random creation of unusual sites for recombination.

Citing Articles

Somatic recombination in adult tissues: What is there to learn?.

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Interindividual variation in mitotic recombination.

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Monitoring exposure to atomic bomb radiation by somatic mutation.

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Low-sister-chromatid-exchange Bloom syndrome cell lines: an important new tool for mapping the basic genetic defect in Bloom syndrome and for unraveling the biology of human tumor development.

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Somatic intragenic recombination within the mutated locus BLM can correct the high sister-chromatid exchange phenotype of Bloom syndrome cells.

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References

Kushiro J, Hirai Y, Kusunoki Y, Kyoizumi S, Kodama Y, Wakisaka A . Development of a flow-cytometric HLA-A locus mutation assay for human peripheral blood lymphocytes. Mutat Res. 1992; 272(1):17-29. DOI: 10.1016/0165-1161(92)90005-7. View

Giulotto E, Mottura A, Giorgi R, De Carli L, Nuzzo F . Frequencies of sister-chromatid exchanges in relation to cell kinetics in lymphocyte cultures. Mutat Res. 1980; 70(3):343-50. DOI: 10.1016/0027-5107(80)90024-x. View

German J, Archibald R, Bloom D . CHROMOSOMAL BREAKAGE IN A RARE AND PROBABLY GENETICALLY DETERMINED SYNDROME OF MAN. Science. 1965; 148(3669):506-7. DOI: 10.1126/science.148.3669.506. View

Wulf H, Kousgaard N, Niebuhr E . Sister-chromatid exchange in childhood in relation to age and sex. Mutat Res. 1986; 174(4):309-12. DOI: 10.1016/0165-7992(86)90052-7. View

Warren S, Schultz R, Chang C, Wade M, Trosko J . Elevated spontaneous mutation rate in Bloom syndrome fibroblasts. Proc Natl Acad Sci U S A. 1981; 78(5):3133-7. PMC: 319514. DOI: 10.1073/pnas.78.5.3133. View

Yanagi Y, Yoshikai Y, Leggett K, Clark S, Aleksander I, Mak T . A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature. 1984; 308(5955):145-9. DOI: 10.1038/308145a0. View

Willis A, Lindahl T . DNA ligase I deficiency in Bloom's syndrome. Nature. 1987; 325(6102):355-7. DOI: 10.1038/325355a0. View

Groden J, German J . Bloom's syndrome. XVIII. Hypermutability at a tandem-repeat locus. Hum Genet. 1992; 90(4):360-7. DOI: 10.1007/BF00220459. View

Shiraishi Y, Taguchi T, Ozawa M, Bamezai R . Different mutations responsible for the elevated sister-chromatid exchange frequencies in Bloom syndrome and X-irradiated B-lymphoblastoid cell lines originating from acute leukemia. Mutat Res. 1989; 211(2):273-8. DOI: 10.1016/0027-5107(89)90010-9. View

10.

Bloom D . Congenital telangiectatic erythema resembling lupus erythematosus in dwarfs; probably a syndrome entity. AMA Am J Dis Child. 1954; 88(6):754-8. View

11.

Langlois R, Bigbee W, Jensen R, German J . Evidence for increased in vivo mutation and somatic recombination in Bloom's syndrome. Proc Natl Acad Sci U S A. 1989; 86(2):670-4. PMC: 286535. DOI: 10.1073/pnas.86.2.670. View

12.

Chan J, Becker F, German J, Ray J . Altered DNA ligase I activity in Bloom's syndrome cells. Nature. 1987; 325(6102):357-9. DOI: 10.1038/325357a0. View

13.

German J . CYTOLOGICAL EVIDENCE FOR CROSSING-OVER IN VITRO IN HUMAN LYMPHOID CELLS. Science. 1964; 144(3616):298-301. DOI: 10.1126/science.144.3616.298. View

14.

Ziegler A, Field L, Sakaguchi A . Report of the committee on the genetic constitution of chromosome 6. Cytogenet Cell Genet. 1990; 55(1-4):118-21. DOI: 10.1159/000133002. View

15.

Heartlein M, Tsuji H, LATT S . 5-Bromodeoxyuridine-dependent increase in sister chromatid exchange formation in Bloom's syndrome is associated with reduction in topoisomerase II activity. Exp Cell Res. 1987; 169(1):245-54. DOI: 10.1016/0014-4827(87)90242-4. View

16.

Olaisen B, Sakaguchi A, Naylor S . Report of the committee on the genetic constitution of chromosomes 5 and 6. Cytogenet Cell Genet. 1987; 46(1-4):147-69. DOI: 10.1159/000132475. View

17.

Grist S, McCarron M, Kutlaca A, Turner D, Morley A . In vivo human somatic mutation: frequency and spectrum with age. Mutat Res. 1992; 266(2):189-96. DOI: 10.1016/0027-5107(92)90186-6. View

18.

Morton N . Gene maps and location databases. Ann Hum Genet. 1991; 55(3):235-41. DOI: 10.1111/j.1469-1809.1991.tb00418.x. View

19.

Morley A, Grist S, Turner D, Kutlaca A, Bennett G . Molecular nature of in vivo mutations in human cells at the autosomal HLA-A locus. Cancer Res. 1990; 50(15):4584-7. View

20.

Seal G, Brech K, Karp S, Cool B, Sirover M . Immunological lesions in human uracil DNA glycosylase: association with Bloom syndrome. Proc Natl Acad Sci U S A. 1988; 85(7):2339-43. PMC: 279987. DOI: 10.1073/pnas.85.7.2339. View