Secondary chromosomal aberrations were surveyed in nonHodgkin's lymphomas (NHL) reported in the literature with one of the following, presently recognized, primary abnormalities: t(2;5), +3, t(3;14), del(6q), t(8;14), t(9;22), t(11;14), del(11q), +12, inv(14), t(14;18), +X, and -Y. Of 2,175 NHLs with clonal karyotypic changes, 908 (42%) had one of the 13 selected primary chromosome rearrangements, and 670 (74%) of these lymphomas displayed additional abnormalities. The type and frequency of the secondary aberrations were ascertained and then correlated with both the type of primary abnormality and morphologic subtype; low-, intermediate-, and high-grade according to the Working Formulation. The incidence of secondary aberrations differed not only among the primary abnormality subgroups, from O% in del(11q) NHLs to 93% in t(3;14) lymphomas (P < .001), but also between B- and T-cell NHLs (78% versus 55%, P < .001) and among the different histologic subgroups: 66% in low-, 85% in intermediate-, and 71% in high-grade lymphomas (P < .001). The mean number of secondary changes per case also varied among the primary abnormalities, from none in del(11q) NHLs to 12.0 in inv(14) lymphomas (P < .001), and among the morphologic subtypes: 4.6 in low-, 6.7 in intermediate-, and 3.6 in high-grade NHL (P < .001). Recurrent secondary aberrations were found in 6 of the 13 primary abnormality subgroups: t(2;5), t(3;14), t(8;14), t(11;14), inv(14), and t(14;18). The most frequent secondary aberrations were +X, -Y, dup(1q), del(6q). +7, and +12. The breakpoints of the dup(1q) and del(6q) varied both within and among the primary abnormalities; the most frequent imbalances were a gain of 1q23-31 and losses of 6q21, 6q23, and 6q25. Other common imbalances were deletions of 1q31-36, 1q31-44, 2q34-37, 7q35-36, 9p22-24, 11q23-25, 13q13-21, and duplication of 12q13-22. The distribution of the secondary changes was clearly nonrandom with the most common anomalies being -Y and +7 in t(2;5); +X, del(6q), and +7 in t(3;14); dup(1q) and +7 in t(8;14); -Y, del(6q), and -13 in t(11;14); del(6q), -17, and -18 in inv(14); and del(6q), +7, and +12 in t(14;18) NHLs. In general, the secondary aberrations were similar in lymphomas of different histologic subtypes but with the same primary abnormality, although some significant differences were discerned: +3, del(6q), +7, and +18 were more common (P < .01) in intermediate-grade than in high-grade t(8;14) NHLs; monosomy 13 occurred only in intermediate-grade t(11;14) NHLs (P < .05); and +7 and t(8;14)/t(8;22) were more frequent IP < .01 and P < .001, respectively) in high-grade than in low- and intermediate-grade t(14;18) NHLs. The chromosome bands most frequently involved in secondary changes were 8q24 in t(2;5); 1q21, 9p24, and 14q32 in t(3;14); 1q21 and 1q32 in t(8;14); 6q15 in t(11;14); 6q15 in inv(14); and 1p36, 1q21, 6q21, and 8q24 in t(14;18) NHLs. We conclude that secondary abnormalities in NHL are nonrandomly distributed throughout the genome, that the acquisition of additional aberrations is associated with lymphoma progression, that the patterns of secondary changes differ among different primary abnormality groups, and that the pathogenetically essential molecular consequences of the secondary changes most likely are genomic imbalance, ie, gain or loss of genetic material, rather than rearrangements of specific genes. (C) 1995 by The American Society of Hematology.
