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 prolymph ocytic 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 br eakpoints 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 d erived from 8p11-p12 using fluorescence in situ hybridization (FISH). Analy sis of FISH results showed that 8p11-p12 breakpoints cluster into two regio ns. The first region is telomeric to YAC 899e2, which contains the fibrobla st 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 e ither side of YAC 806e9, flanked by YAC 940f10 distally and YAC 910d7 proxi mally, the latter containing the MOZ gene, These findings showed that a seg ment of 8p was still present in the isodicentric, bat the pattern of cluste ring does not seem to correspond to a breakpoint affecting a single gene. T he clustering regions are likely to be hot spots for recombination and resu lt in idic(8)(p11) and 8p+. These changes point to the pathogenesis of T-PL L involving deletion of a gene sequence on 8p and/or gain of a copy of Bq. (C) 2000 Elsevier Science Inc. All rights reserved.