title: Persisting ring chromosomes detected by mFISH in lymphocytes of a cancer patient-a case report.
abstract: 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. Blood samples were irradiated ex vivo with Cs-137 γ-rays (0.7Gy/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 characterise 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). 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 chromosome 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 localised at 8p21.2-22. The breakpoint at the q arm turned out to be distal from the MYC locus at 8q23-24. We hypothesise that the ring chromosome 8 has been developed during 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 cycling progenitor cells that permit cell survival and proliferation.
authors.affiliation: Department of Safety and Radiation Protection, Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany. Electronic address: sa.schmitz@fz-juelich.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schmitz
authors.forename: Michael
authors.initials: M
authors.lastname: Pinkawa
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Eble
authors.forename: Ralf
authors.initials: R
authors.lastname: Kriehuber
mesh_terms: D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001773:Blood Cells / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000187:drug effects*; D020223:Chromosome Painting; D002898:Chromosomes, Human, Pair 8 / Q000187:drug effects / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage; D005720:Gamma Rays; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D002955:Leucovorin / Q000008:administration & dosage; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008677:Metaphase; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D012303:Ring Chromosomes
chemical_list: D002955:Leucovorin; D005472:Fluorouracil
keywords: 5-FU; Cancer patient; Clonal aberration; Long term persistence; Radiotherapy; Ring chromosome; mFISH