PMID- 12203776
OWN - NLM
STAT- MEDLINE
DCOM- 20021004
LR  - 20071115
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 35
IP  - 2
DP  - 2002 Oct
TI  - Multicolor COBRA-FISH analysis of chronic myeloid leukemia reveals novel cryptic 
      balanced translocations during disease progression.
PG  - 127-37
AB  - During the initial indolent chronic phase of chronic myeloid leukemia (CML), the 
      t(9;22)(q34;q11), resulting in the Philadelphia chromosome (Ph), is usually the 
      sole cytogenetic anomaly, but as the disease progresses into the accelerated 
      phase (AP), and eventually into aggressive blast crisis (BC), secondary 
      aberrations, mainly unbalanced changes such as +8, i(17q), and +Ph, are frequent. 
      To date, molecular genetic studies of CML BC have mainly focused on alterations 
      of well-known tumor-suppressor genes (e.g., TP53, CDKN2A, and RB1) and oncogenes 
      (e.g., RAS and MYC), whereas limited knowledge is available about the molecular 
      genetic correlates of the unbalanced chromosomal abnormalities. Balanced 
      secondary changes are rare in CML AP/BC, but it is not known whether cryptic 
      chromosomal translocations, generating fusion genes, may be responsible for 
      disease progression in a subgroup of CML. To address this issue, we used 
      multicolor combined binary ratio fluorescence in situ hybridization (FISH), which 
      allows the simultaneous visualization of all 24 chromosomes in different colors, 
      verified by locus-specific FISH in a series of 33 CML cases. Two cryptic balanced 
      translocations, t(7;17)(q32-34;q23) and t(7;17)(p15;q23), were found in two of 
      the five cases showing the t(9;22) as the only cytogenetic change. Using several 
      BAC clones, the breakpoints at 17q23 in both cases were mapped within a 350-kb 
      region. In the case with the 7p15 breakpoint, a BAC clone containing the HOXA 
      gene cluster displayed a split signal, suggesting a possible creation of a fusion 
      gene involving a member of the HOXA family. Furthermore, one case with a 
      partially cryptic t(9;11)(p21-22;q23) and an MLL rearrangement as well as a 
      previously unreported t(3;10)(p22;p12-13) were identified. Altogether, a refined 
      karyotypic description was achieved in 12 (36%) of the 33 investigated cases, 
      illustrating the value of using multicolor FISH for identifying pathogenetically 
      important aberrations in CML AP/BC.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Barbouti, Aikaterini
AU  - Barbouti A
AD  - Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. 
      Aikaterini.Barmpouti@klingen.lu.se
FAU - Johansson, Bertil
AU  - Johansson B
FAU - Hoglund, Mattias
AU  - Hoglund M
FAU - Mauritzson, Nils
AU  - Mauritzson N
FAU - Strombeck, Bodil
AU  - Strombeck B
FAU - Nilsson, Per-Gunnar
AU  - Nilsson PG
FAU - Tanke, Hans J
AU  - Tanke HJ
FAU - Hagemeijer, Anne
AU  - Hagemeijer A
FAU - Mitelman, Felix
AU  - Mitelman F
FAU - Fioretos, Thoas
AU  - Fioretos T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Chromosome Aberrations
MH  - Chromosome Banding
MH  - Chromosome Painting
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Karyotyping
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Translocation, Genetic/*genetics
EDAT- 2002/08/31 10:00
MHDA- 2002/10/09 04:00
CRDT- 2002/08/31 10:00
PHST- 2002/08/31 10:00 [pubmed]
PHST- 2002/10/09 04:00 [medline]
PHST- 2002/08/31 10:00 [entrez]
AID - 10.1002/gcc.10099 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2002 Oct;35(2):127-37. doi: 10.1002/gcc.10099.