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Diagnosis of Fanconi Anaemia by ionising radiation- or mitomycin C-induced micronuclei

(2018) DNA REPAIR. 61. p.17-24
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Abstract
Fanconi Anaemia (FA) is an autosomal recessive disorder characterised by defects in DNA repair, associated with chromosomal instability and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC). The FA repair pathway involves complex DNA repair mechanisms crucial for genomic stability. Deficiencies in DNA repair genes give rise to chromosomal radiosensitivity. FA patients have shown increased clinical radio sensitivity by exhibiting adverse normal tissue side-effects. The study aimed to investigate chromosomal radiosensitivity of homozygous and heterozygous carriers of FA mutations using three micronucleus (MN) assays. The GO and S/G2 MN assays are cytogenetic assays to evaluate DNA damage induced by ionising radiation in different phases of the cell cycle. The MMC MN assay detects DNA damage induced by a crosslinking agent in the GO phase. Patients with a clinical diagnosis of FA and their parents were screened for the complete coding region of 20 FA genes. Blood samples of all FA patients and parents were exposed to ionising radiation of 2 and 4 Gy. Chromosomal radiosensitivity was evaluated in the GO and S/G2 phase. Most of our patients were homozygous for the founder mutation FANCG c.637_643delTACCGCC; p.(Tyr213Lysfs*6) while one patient was compound heterozygous for FANCG c.637_643delTACCGCC and FANCG c.1379G > A, p.(Gly460Asp), a novel missense mutation. Another patient was compound heterozygous for two deleterious FANCA mutations. In FA patients, the GO- and S/G2-MN assays show significantly increased chromosomal radiosensitivity and genomic instability. Moreover, chromosomal damage was significantly elevated in MMC treated FA cells. We also observed an increase in chromosomal radiosensitivity and genomic instability in the parents using 3 assays. The effect was significant using the MMC MN assay. The MMC MN assay is advantageous as it is less labour intense, time effective and has potential as a reliable alternative method for detecting FA patients from parents and controls.
Keywords
Fanconi Anaemia, DNA repair, Chromosomal radiosensitivity, Genomic instability, Radiosensitivity, BREAST-CANCER PATIENTS, VITRO CHROMOSOMAL RADIOSENSITIVITY, C.5101C-GREATER-THAN-T MUTATION, DNA-REPAIR, PATHWAY, BRCA1, RISK, GENE, PROTECTION, BREAKAGE

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MLA
Francies, Flavia Zita, Rosalind Wainwright, Janet Poole, et al. “Diagnosis of Fanconi Anaemia by Ionising Radiation- or Mitomycin C-induced Micronuclei.” DNA REPAIR 61 (2018): 17–24. Print.
APA
Francies, Flavia Zita, Wainwright, R., Poole, J., De Leeneer, K., Coene, I., Wieme, G., Poirel, H. A., et al. (2018). Diagnosis of Fanconi Anaemia by ionising radiation- or mitomycin C-induced micronuclei. DNA REPAIR, 61, 17–24.
Chicago author-date
Francies, Flavia Zita, Rosalind Wainwright, Janet Poole, Kim De Leeneer, Ilse Coene, Greet Wieme, Hélène A Poirel, et al. 2018. “Diagnosis of Fanconi Anaemia by Ionising Radiation- or Mitomycin C-induced Micronuclei.” Dna Repair 61: 17–24.
Chicago author-date (all authors)
Francies, Flavia Zita, Rosalind Wainwright, Janet Poole, Kim De Leeneer, Ilse Coene, Greet Wieme, Hélène A Poirel, Bénédicte Brichard, Stephanie Vermeulen, Anne Vral, Jacobus Slabbert, Kathleen Claes, and Ans Baeyens. 2018. “Diagnosis of Fanconi Anaemia by Ionising Radiation- or Mitomycin C-induced Micronuclei.” Dna Repair 61: 17–24.
Vancouver
1.
Francies FZ, Wainwright R, Poole J, De Leeneer K, Coene I, Wieme G, et al. Diagnosis of Fanconi Anaemia by ionising radiation- or mitomycin C-induced micronuclei. DNA REPAIR. 2018;61:17–24.
IEEE
[1]
F. Z. Francies et al., “Diagnosis of Fanconi Anaemia by ionising radiation- or mitomycin C-induced micronuclei,” DNA REPAIR, vol. 61, pp. 17–24, 2018.
@article{8537947,
  abstract     = {{Fanconi Anaemia (FA) is an autosomal recessive disorder characterised by defects in DNA repair, associated with chromosomal instability and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC). The FA repair pathway involves complex DNA repair mechanisms crucial for genomic stability. Deficiencies in DNA repair genes give rise to chromosomal radiosensitivity. FA patients have shown increased clinical radio sensitivity by exhibiting adverse normal tissue side-effects. The study aimed to investigate chromosomal radiosensitivity of homozygous and heterozygous carriers of FA mutations using three micronucleus (MN) assays. The GO and S/G2 MN assays are cytogenetic assays to evaluate DNA damage induced by ionising radiation in different phases of the cell cycle. The MMC MN assay detects DNA damage induced by a crosslinking agent in the GO phase. Patients with a clinical diagnosis of FA and their parents were screened for the complete coding region of 20 FA genes. Blood samples of all FA patients and parents were exposed to ionising radiation of 2 and 4 Gy. Chromosomal radiosensitivity was evaluated in the GO and S/G2 phase. Most of our patients were homozygous for the founder mutation FANCG c.637_643delTACCGCC; p.(Tyr213Lysfs*6) while one patient was compound heterozygous for FANCG c.637_643delTACCGCC and FANCG c.1379G > A, p.(Gly460Asp), a novel missense mutation. Another patient was compound heterozygous for two deleterious FANCA mutations. In FA patients, the GO- and S/G2-MN assays show significantly increased chromosomal radiosensitivity and genomic instability. Moreover, chromosomal damage was significantly elevated in MMC treated FA cells. We also observed an increase in chromosomal radiosensitivity and genomic instability in the parents using 3 assays. The effect was significant using the MMC MN assay. The MMC MN assay is advantageous as it is less labour intense, time effective and has potential as a reliable alternative method for detecting FA patients from parents and controls.}},
  author       = {{Francies, Flavia Zita and Wainwright, Rosalind and Poole, Janet and De Leeneer, Kim and Coene, Ilse and Wieme, Greet and Poirel, Hélène A and Brichard, Bénédicte and Vermeulen, Stephanie and Vral, Anne and Slabbert, Jacobus and Claes, Kathleen and Baeyens, Ans}},
  issn         = {{1568-7864}},
  journal      = {{DNA REPAIR}},
  keywords     = {{Fanconi Anaemia,DNA repair,Chromosomal radiosensitivity,Genomic instability,Radiosensitivity,BREAST-CANCER PATIENTS,VITRO CHROMOSOMAL RADIOSENSITIVITY,C.5101C-GREATER-THAN-T MUTATION,DNA-REPAIR,PATHWAY,BRCA1,RISK,GENE,PROTECTION,BREAKAGE}},
  language     = {{eng}},
  pages        = {{17--24}},
  title        = {{Diagnosis of Fanconi Anaemia by ionising radiation- or mitomycin C-induced micronuclei}},
  url          = {{http://dx.doi.org/10.1016/j.dnarep.2017.11.001}},
  volume       = {{61}},
  year         = {{2018}},
}

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