PMID- 11480561 OWN - NLM STAT- MEDLINE DCOM- 20010816 LR - 20190915 IS - 0887-6924 (Print) IS - 0887-6924 (Linking) VI - 15 IP - 8 DP - 2001 Aug TI - Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones. PG - 1193-202 AB - During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one with biphenotypic leukemia) who showed more complicated rearrangements than we had expected from conventional cytogenetic study. In six patients, multiple breaks occurred in small segments of 12p with subsequent translocations and insertions of these segments into other chromosomes, sometimes to unexpected regions. In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. It is likely that multiple chromosome breaks were induced through mutagens used in chemo/ radiotherapy, and are associated with a sub-group of patients with an extremely bad prognosis. FAU - Sato, Y AU - Sato Y AD - Department of Clinical Pathology, Research Institute of International Medical Center of Japan, Tokyo. FAU - Kobayashi, H AU - Kobayashi H FAU - Suto, Y AU - Suto Y FAU - Olney, H J AU - Olney HJ FAU - Davis, E M AU - Davis EM FAU - Super, H G AU - Super HG FAU - Espinosa, R 3rd AU - Espinosa R 3rd FAU - Le Beau, M M AU - Le Beau MM FAU - Rowley, J D AU - Rowley JD LA - eng GR - CA40046/CA/NCI NIH HHS/United States GR - CA42557/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Leukemia JT - Leukemia JID - 8704895 SB - IM MH - *Chromosome Fragility MH - *Chromosomes, Human, Pair 12 MH - Gene Rearrangement MH - Hematologic Neoplasms/*genetics MH - Humans EDAT- 2001/08/02 10:00 MHDA- 2001/08/17 10:01 CRDT- 2001/08/02 10:00 PHST- 2001/08/02 10:00 [pubmed] PHST- 2001/08/17 10:01 [medline] PHST- 2001/08/02 10:00 [entrez] AID - 10.1038/sj.leu.2402188 [doi] PST - ppublish SO - Leukemia. 2001 Aug;15(8):1193-202. doi: 10.1038/sj.leu.2402188.