PMID- 9737690
OWN - NLM
STAT- MEDLINE
DCOM- 19980924
LR  - 20190915
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 12
IP  - 9
DP  - 1998 Sep
TI  - Molecular characterization of jumping translocations reveals spatial and temporal 
      breakpoint heterogeneity.
PG  - 1411-6
AB  - Jumping translocations (JT) are characterized by the relocalization of the same 
      part of a donor to several recipient chromosomes. Although JT occasionally are 
      constitutional, most are associated with hematologic malignancies. In such cases, 
      JT usually arise during disease progression and are associated with poor 
      prognosis. Despite its clinical importance, this cytogenetic phenomenon has not 
      been characterized at the molecular level. We have analyzed JT in a juvenile 
      chronic myelomonocytic leukemia that subsequently transformed to an acute myeloid 
      leukemia. Detailed fluorescence in situ hybridization (FISH) analyses showed that 
      the cytogenetically identical donor breakpoint at 3q21 was highly heterogeneous. 
      In fact, more than 10 distinct breakpoints, four of which mapped within YACs, 
      were identified. Analyses of samples during disease progression showed that the 
      breakpoint complexity decreased, indicating clonal selection. Hence, the 3q21 
      breakpoints displayed a spatial as well as a temporal heterogeneity, revealing 
      that JT are highly unstable, showing great variation in the size of donor 
      segment. The breaks at the recipient chromosomes were mapped within the 
      subtelomeric regions. The general telomere length was not affected and an 
      underlying replication error resulting in microsatellite instability was 
      excluded. We conclude that the emergence of JT is unlikely to cause fusion genes 
      or to affect the expression of genes located in the breakpoint regions. The 
      identification of YACs spanning the breakpoints, ie, YACs 913c7, 937g5, 948c2 and 
      955g1, may facilitate the isolation of DNA sequences leading to a genetic 
      instability associated with the origin of multiple translocations.
FAU - Andreasson, P
AU  - Andreasson P
AD  - Department of Clinical Genetics, Lund University Hospital, Sweden.
FAU - Hoglund, M
AU  - Hoglund M
FAU - Jonson, T
AU  - Jonson T
FAU - Bekassy, A
AU  - Bekassy A
FAU - Mitelman, F
AU  - Mitelman F
FAU - Johansson, B
AU  - Johansson B
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
SB  - IM
MH  - Child, Preschool
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Chromosomes, Human, Pair 15/genetics
MH  - Chromosomes, Human, Pair 22/genetics
MH  - Chromosomes, Human, Pair 3/*genetics
MH  - Chromosomes, Human, Pair 7/genetics
MH  - Fatal Outcome
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Leukemia, Myelomonocytic, Chronic/*genetics
MH  - Male
MH  - Microsatellite Repeats/genetics
MH  - Translocation, Genetic/*genetics
EDAT- 1998/09/16 00:00
MHDA- 1998/09/16 00:01
CRDT- 1998/09/16 00:00
PHST- 1998/09/16 00:00 [pubmed]
PHST- 1998/09/16 00:01 [medline]
PHST- 1998/09/16 00:00 [entrez]
AID - 10.1038/sj.leu.2401108 [doi]
PST - ppublish
SO  - Leukemia. 1998 Sep;12(9):1411-6. doi: 10.1038/sj.leu.2401108.