Comparative genomic hybridization analysis of natural killer cell lymphoma/leukemia - Recognition of consistent patterns of generic alterations

Putative natural killer (NK) cell lymphoma/leukemia is a rare group of rece ntly characterized hematolymphoid malignancies. They are highly aggressive and frequently present in extranodal sites, including the nasal area and th e upper aerodigestive system, and nonnasal areas such as the skin and the g astrointestinal tract. According to clinicopathological features, they can be classified into nasal NK cell lymphoma, nasal-type NK cell lymphoma occu rring in nonnasal areas, and NK cell lymphoma/leukemia. Genetic alterations in NK cell lymphoma/leukemia are not well defined. In this study, we have performed comparative genomic hybridization (CGH) on DNA extracted from fre sh or frozen tissues of 10 patients with NK cell lymphoma/leukemia. They co mprised four nasal NK cell lymphomas, one nasal-type NK cell lymphoma, and five NK cell lymphomas/leukemias. CGH showed frequent deletions at 6q16-q27 (four cases), 13q14-q34 (three cases), 11q22-q25 (two cases), 17p13 (two c ases), and loss of the whole chromosome X (two cases). DNA amplification wa s observed in a majority of the chromosomes. Five cases showed DNA gains at region 1p32-pter, Frequent DNA gains were also found in chromosomes 6p, 11 q, 12q, 17q, 19p, 20q, and Xp (three cases each). Interestingly, DNA gains were more frequent in nasal/nasal-type NK cell lymphomas than Mt cell lymph oma/leukemia. These genetic alterations correlated well with karyotypic fea tures found in some of the cases. The frequent DNA losses at 6q and 13q sug gest that the presence of tumor suppressor genes at these regions is import ant in NK cell transformation. In addition to establishing novel patterns o f genomic imbalances in these rare NK cell malignancies, which may be targe ts for future molecular analysis, this study also provides important inform ation on genetic alterations in NK cell lymphomas that may be useful in def ining their positions in current lymphoma classification schemes, which are increasingly focusing on phenotypic and genotypic correlations.