Unusual breakpoint distribution of 8p abnormalities in T-prolymphocytic leukemia: a study with YACS mapping to 8p11-p12.
Chromosome 8 abnormalities are seen in 80% of patients with T-cell prolymphocytic leukemia (T-PLL). The abnormalities described are idic(8)(p11),t(8;8)(p11;q12),+8, and 8p+ with the involvement of 8p. To localize 8p11-p12 breakpoints in T-PLL, metaphases from seven cases were karyotyped. Those with idic(8)(p11) and add(8)(p11) were probed with a panel of contiguous YACs derived from 8p11-p12 using fluorescence in situ hybridization (FISH). Analysis of FISH results showed that 8p11-p12 breakpoints cluster into two regions. The first region is telomeric to YAC 899e2, which contains the fibroblast growth factor receptor-1 gene (FGFR1) and appears to cluster within a 1.5-MB YAC 807a2. The second region is more centromeric with breakpoints on either side of YAC 806e9, flanked by YAC 940f10 distally and YAC 910d7 proximally, the latter containing the MOZ gene. These findings showed that a segment of 8p was still present in the isodicentric, but the pattern of clustering does not seem to correspond to a breakpoint affecting a single gene. The clustering regions are likely to be hot spots for recombination and result in idic(8)(p11) and 8p+. These changes point to the pathogenesis of T-PLL involving deletion of a gene sequence on 8p and/or gain of a copy of 8q.
Sorour
A
A
Academic Department of Haematology and Cytogenetics, Royal Marsden NHS Trust, The Institute of Cancer Research, London, United Kingdom.
Brito-Babapulle
V
V
Smedley
D
D
Yuille
M
M
Catovsky
D
D
D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002898:Chromosomes, Human, Pair 8; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015463:Leukemia, Prolymphocytic / Q000235:genetics*; D015458:Leukemia, T-Cell / Q000235:genetics*