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. 2006 Jan 30;94(2):308-10.
doi: 10.1038/sj.bjc.6602912.

Increased level of chromosomal damage after irradiation of lymphocytes from BRCA1 mutation carriers

Z Kote-Jarai  1 , A Salmon, T Mengitsu, M Copeland, A Ardern-Jones, I Locke, S Shanley, B Summersgill, Y-J Lu, J Shipley, R Eeles
Affiliations

Increased level of chromosomal damage after irradiation of lymphocytes from BRCA1 mutation carriers

Z Kote-Jarai et al. Br J Cancer. .

Abstract

Deleterious mutations in the BRCA1 gene predispose women to an increased risk of breast and ovarian cancer. Many functional studies have suggested that BRCA1 has a role in DNA damage repair and failure in the DNA damage response pathway often leads to the accumulation of chromosomal aberrations. Here, we have compared normal lymphocytes with those heterozygous for a BRCA1 mutation. Short-term cultures were irradiated (8Gy) using a high dose rate and subsequently metaphases were analysed by 24-colour chromosome painting (M-FISH). We scored the chromosomal rearrangements in the metaphases from five BRCA1 mutation carriers and from five noncarrier control samples 6 days after irradiation. A significantly higher level of chromosomal damage was detected in the lymphocytes heterozygous for BRCA1 mutations compared with normal controls; the average number of aberrations per mitosis was 3.48 compared with 1.62 in controls (P=0.0001). This provides new evidence that heterozygous mutation carriers have a different response to DNA damage compared with noncarriers and that BRCA1 has a role in DNA damage surveillance. Our finding has implications for treatment and screening of BRCA1 mutation carriers using modalities that involve irradiation.

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Figures

Figure 1
Figure 1
M-FISH analysis of a metaphase spread from a BRCA1 carrier lymphocyte 6 days after high dose ionizing irradiation (8 Gy total). White arrows show the chromosomal aberrations.
See this image and copyright information in PMC

References

    1. Arlt MF, Xu B, Durkin SG, Casper AM, Kastan MB, Glover TW (2004) BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function. Mol Cell Biol 24: 6701–6709 - PMC - PubMed
    1. Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS, Wang W, Kashanchi F, Shiekhattar R (2000) BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer. Cell 102: 257–265 - PubMed
    1. Buchholz TA, Wu X, Hussain A, Tucker SL, Mills GB, Haffty B, Bergh S, Story M, Geara FB, Brock WA (2002) Evidence of haplotype insufficiency in human cells containing a germline mutation in BRCA1 or BRCA2. Int J Cancer 97: 557–561 - PubMed
    1. Darby SC, McGale P, Taylor CW, Peto R (2005) Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300 000 women in US SEER cancer registries. Lancet Oncol 6: 557–565 - PubMed
    1. Dasu A, Toma-Dasu I, Oloffson J, Karlsson M (2005) The use of risk estimation models for the induction of secondary cancers following radiotherapy. Acta Oncol 44: 339–347 - PubMed