Aberrations of chromosomal bands 1p36 and 1q11-q23 are among the most common chromosomal alterations in non-Hodgkin lymphoma (NHL). In this study, 16 cases of NHL showing recurrent unbalanced translocation t(1;1)(p36;q11-23) by G-band analysis were selected for further analysis. To delineate the exact breakpoints, multicolor band analysis for chromosome 1 (M-BAND1), and locus-specific fluorescence in situ hybridization (LS-FISH) using human genome designated BAC clones were performed. In all but one dicentric case, the breakpoint was determined to involve chromosomal bands 1p36.3 and 1q21.1-2. LS-FISH analysis for the TP73, MEL1, SKI, and CASP9 loci at 1p36, and the loci IRTA1, IRTA2, BCL9, AF1Q, JTB, and MUC1 at 1q21, verified the MBAND1 results and further delineated the breakpoints. In band 1p36, two hybridization patterns were observed, one involving deletions of MEL1, TP73, and SKI, but not CASP9, and the second involving a breakpoint telomeric to TP73. In region 1q21, four hybridization patterns were observed, the first involving duplication/translocation of all five genes; the second involving duplication/translocation of BCL9, AF1Q, JTB, and MUC1; the third involving duplication/translocation of AF1Q, JTB, and MUC1; and the fourth with a breakpoint telomeric to MUC1. Using an alpha-satellite probe for chromosome 1 (D1Z5), centromeric involvement in the unbalanced translocation t(1;1)(p36.3;q21.1-2) was excluded in all but the one dicentric case, that is, dic(1;1)(p36.3;q10). In conclusion, deletion of 1p36 and duplication of 1q21 through formation of an unbalanced translocation t(1;1)(p36.3;q21.1-2) is a non-random event in NHL, suggesting a deletion-duplication mechanism involved in lymphoma progression and justifying further systematic research.
Copyright 2003 Wiley-Liss, Inc.