Multicolor-FISH analysis of a natural killer cell line (NK-92)

Relatively little is known about the cytogenetics of natural killer (NK) neoplasms, and the emergence of recurrent structural alterations involving specific chromosomal breakpoints is still in its infancy. This gap has doubtless hampered identification of the oncogene alterations posited to underly NK tumors. We describe in detail the cytogenetic rearrangements present in a cytotoxic NK cell line (NK-92) established from a patient with large granular lymphocyte (LGL) lymphoma. The NK-92 cell line is one of very few cytotoxic NK cell lines described and the first to be used clinically. Cytogenetic analysis was performed independently using two multicolor-fluorescence in situ hybridization (M-FISH) systems, the first M-FISH study of a cell line derived from a NK neoplasm. Several non-random cytogenetic features previously reported in NK cells were, thus, identified, including rearrangements of chromosomes 7 and 17, along with breakpoints at 11q23, 12q12 and 8p22/23. FISH revealed that NK-92 cells carry multiple rearrangements with distinct breakpoints at 8p resembling those previously described in NK lymphoma. Our data strengthen the claim of NK-92 to model NK neoplasms and highlight this cell line as a potential resource for mining relevant oncogenic changes therein.