Conference Presentation (Invited) FZJ-2018-00845

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Persisting ring chromosomes detected by mFISH in Lymphocytes of a cancer patient - a case study

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2013

16th Annual Meeting of the German Society for Biological Radiation Research, GBS, DarmstadtDarmstadt, Germay, 25 Sep 2013 - 27 Sep 20132013-09-252013-09-27

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Abstract: Background: We report the case of an 84 years old prostate cancer patient with severe side effects after radiotherapy in 2006. He was cytogenetically analysed in 2009 and in 2012 in a comparative study for individual radiosensitivity of prostate cancer patients. No other patient had clonal aberrations, but this patient showed ring chromosomes in the range of 21-25 % of lymphocytes. He received 5 cycles of 5-fluorouracil/folic acid for chemotherapy of sigmoid colon carcinoma in 2003, three years before radiotherapy of prostate cancer.Material und Methods: Blood samples were irradiated ex vivo with Cs-137 γ-rays (0.7 Gy/min) in the G0-phase of the cell cycle. 100 FISH painted metaphases were analysed for the control and the irradiated samples each. Multicolour in situ hybridisation techniques like mFISH and mBand as well as MYC locus, telomere and centromere painting probes were used to characterize ring metaphases. Metaphase search and autocapture was performed with a Zeiss Axioplan 2 imaging microscope followed by scoring and image analysis using Metafer 4/ISIS software (MetaSystems).Results: In 2009 chromosome 8 rings were found in about 25 % of lymphocytes. Rings were stable over time and increased to about 30 % until 2012. The ring chro-mosome 8 always lacked telomere signals and a small amount of rings displayed up to four centromere signals. In aberrant metaphases 8pter and 8qter were either translocated or deleted. Further analyses revealed that the breakpoint at the p arm is localized at 8p21.2-22. The breakpoint at the q arm turned out to be distal from the MYC locus at 8q23-24.Conclusion: We hypothesize that the ring chromosome 8 has been developed dur-ing the 5 FU/folic acid treatments in 2003. The long term persistence might be due to clonal expansion of a damaged but viable hematopoietic stem cell giving rise to cy-cling progenitor cells that permit cell survival and proliferation.Funded by Dr. Erich-Schmitt-Stiftung

Keyword(s): Biology (2nd)


Contributing Institute(s):
  1. Sicherheit und Strahlenschutz, Umgebungsüberwachung,Strahlenbiologie (S-US)
Research Program(s):
  1. 899 - ohne Topic (POF3-899) (POF3-899)

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 Datensatz erzeugt am 2018-01-26, letzte Änderung am 2021-01-29


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