Acquired chromosome rearrangements in human lymphocytes: effect of aging

Prieur, M; Achkar, Walid Al; Aurias, Alain; Couturier, J.; Dutrillaux, Anne-Marie; Dutrillaux, Bernard; Flüry-Hérard, A.; Gerbault-Seureau, M.; Hoffschir, Françoise; Lamoliatte, E.; Lefrançois, D.; Lombard, M.; Muleris, Martine; Ricoul, Michelle; Sabatier, Laure; Viegas‐Péquignot, Evani

doi:10.1007/bf00280554

Cited by 55 publications

(18 citation statements)

References 19 publications

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“…However the effects of gender, ethnicity, and lifestyle factors (such as cigarette smoking) on background translocation yields have been difficult to assess due to small sample sizes [10][11][12][13][14][15]. For many years chromosome aberration frequencies have been known to increase with age [16][17][18][19][20], but the relationship between translocation frequencies and age has not been well characterized. More precise estimates of background translocation levels in humans are needed [21,22].…”

Section: Introductionmentioning

confidence: 99%

International study of factors affecting human chromosome translocations

Sigurdson

Hauptmann

et al. 2008

Mutation Research/Genetic Toxicology and Environmental Mutagene

122

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Abstract*Correspondence, page proofs, and reprint requests to: James D. Tucker, Ph.D., Department of Biological Sciences, 1370 Biological Sciences Building, 5047 Gullen Mall, Wayne State University, Detroit, TEL: (313) 577-2783, FAX: (313) 577-3602, EMAIL: E-mail: jtucker@biology.biosci.wayne.edu. z Retired Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from sixteen laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages vs. a linear relationship (p <0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR) = 1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes. NIH Public Access

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Section: Introductionmentioning

confidence: 99%

International study of factors affecting human chromosome translocations

Sigurdson

Hauptmann

et al. 2008

Mutation Research/Genetic Toxicology and Environmental Mutagene

122

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“…Metaphases carrying at least one chromosomal aberration ranged from 12 to 36%, with an average of 21.6% for group A and from 13 to 31%, with an average of 19.7% for group B. Percentages of abnormal metaphases (Table 111) are much lower in the 2 untreated control series A (1.2%) and B (3.5%) (Aurias et al, 1985;Marlhens et al, 1986;Prieur et al, 1988). In contrast, percentages obtained from the 2 groups of treated patients with S-ANLL were similar to those observed in lymphocytes from patients (control C) treated with melphalan without S-ANLL (21.5%) (Mamuris et al, 1989~).…”

Section: Resultsmentioning

confidence: 93%

“…The only recurrent breakpoints found in untreated controls were 7p14, 7q35, 14q12 and 14qter for both translocations and inversions (Prieur et al, 1988;Aurias et al, 1985) and 9q12 for deletions (Marlhens et al, 1986). These 5 bands were not overaffected in our sample.…”

Section: Discussionmentioning

confidence: 96%

Specific chromosomal mutagenesis observed in stimulated lymphocytes from patients with S‐ANLL

Mamuris

Dumont²,

Dutrillaux

et al. 1990

Intl Journal of Cancer

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An analysis of R-banded PHA-stimulated lymphocytes from 13 patients with secondary acute non-lymphocytic leukemia (S-ANLL) following breast cancer or lymphoma, and treatment by alkylating agents and/or radiotherapy, is reported. We found that chromosomes 5, 7, 11 and 17 are over-involved in structural rearrangements. These anomalies are similar to those observed in the same categories of patients without S-ANLL, and after in vitro treatment of normal lymphocytes by the alkylating agent melphalan. These anomalies are thus likely to be induced by treatment, independently of S-ANLL. However, the same chromosomes (5, 7, 11 and 17) are recurrently deficient in leukemic S-ANLL clones. In spite of these similarities, it remains unlikely that the deficiencies observed in leukemic clones were directly induced at the time of treatment. Probably, treatment of primary cancers induces nonrandom mutations of recessive genes located on these chromosomes as also indicated by chromosomal lesions. Various rearrangements including deletions of the homologous normal counterparts may then occur, unmasking mutated recessive genes. The latter stage would be concomitant with the leukemogenic process.

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“…To date, the number of illegitimate recombinations between the TCR genes has been studied in humans [Hecht et al, 1987;Prieur et al, 1988;Tawn, 1988;Lipkowitz et al, 1990;Kobayashi et al, 1991;Musilova et al, 2014], mice [Huang et al, 2007;Bowen et al, 2013], and pigs [Musilova et al, 2014]. We used the same methodological approach as Musilova et al [2014] who showed that the frequencies of translocations involving pig TRA/TRD were significantly higher than the frequencies of corresponding trans-rearrangements involving TRA/TRD in humans.…”

Section: Discussionmentioning

confidence: 99%

“…A low percentage of peripheral blood T lymphocytes in healthy humans carry such illegitimate rearrangements [Hecht et al, 1987;Prieur et al, 1988;Tawn, 1988], and their frequencies have also been assessed in pigs, showing that the incidence is higher in pigs than in humans [Musilova et al, 2014].…”

mentioning

confidence: 99%

Impact of Karyotype Organization on Interlocus Recombination between T Cell Receptor Genes in Equidae

Drbalová

Musilová

Kubı́čková

et al. 2014

Cytogenet Genome Res

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The T cell receptor (TCR) genes (TRA, TRB, TRD and TRG) reside in 3 different chromosomal regions. During the maturation of T lymphocytes, the TCR genes are rearranged by site-specific recombination, a process that also predisposes T cells to aberrant rearrangements. Illegitimate recombination between the TCR genes occurs at a low level in healthy individuals, but this frequency may correlate with the risk of lymphoma. The aim of this work was to investigate interlocus recombination in equids. Illegitimate rearrangements were studied in peripheral blood lymphocytes by FISH with painting and BAC probes and by sequencing of PCR products, and the frequencies of recombination were assessed in horses and 4 other equids. The presence of several trans-rearrangement products between the TRA and TRG genes was verified by PCR in all investigated equids. Frequencies of trans-rearrangements in horses are higher than in humans, and colocalization of the TCR genes on the same chromosome increases the incidence of trans-rearrangements between them. The orientation of the TCR genes does not impact interlocus recombination itself but does affect the viability of cells carrying its products and consequently the number of trans-rearrangements observed in lymphocytes.

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Acquired chromosome rearrangements in human lymphocytes: effect of aging

Cited by 55 publications

References 19 publications

International study of factors affecting human chromosome translocations

International study of factors affecting human chromosome translocations

Specific chromosomal mutagenesis observed in stimulated lymphocytes from patients with S‐ANLL

Impact of Karyotype Organization on Interlocus Recombination between T Cell Receptor Genes in Equidae

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