Combined spectral karyotyping, comparative genomic hybridization, and in vitro apoptyping of a panel of Burkitt's lymphoma-derived B cell lines reveals an unexpected complexity of chromosomal aberrations and a recurrence of specific abnormalities in chemoresistant cell lines.
The comprehensive cytogenetic profiles of a panel of 10 Burkitt's lymphoma (BL)-derived B cell lines, designated Akata, BL-28, BL-41, Daudi, DG-75, Mutu I, Mutu III, Namalwa, Rael, and Ramos, respectively, are reported herein. The unique origin of each cell line was established using multiplex quantitative fluorescence polymerase chain reaction (QF-PCR). Spectral karyotyping (SKY) revealed a large number of structural and numerical chromosomal aberrations, many of which had not been previously identified or resolved by conventional G-banding techniques. Notably, whereas all 10 cell lines harbored the hallmark translocation t(8;14)(q24;q32), no other common structural aberrations were identified, although translocations involving chromosomes 3, 13, and 17 were frequently seen. Moreover, analysis of chromosomal breakpoints by comparative genomic hybridization (CGH) revealed a number of recurring aberrations, such as gain of chromosomes 7 and 20, gains of regions at 2p, 3q, 13q and 16q, and losses at 3p, 4q and 17p. In addition, apoptyping (i.e. determination of in vitro responses to apoptosis stimulation) of the cell lines suggested specific association patterns between karyotypic changes (e.g. translocations involving 17p, and gains of portions of chromosomes 7 and 20) and resistance to the chemotherapeutic agent, etoposide. The current molecular cytogenetic characterization of 10 BL cell lines has thus identified several novel sites of rearrangements; moreover, the combined karyotyping and functional assessment (apoptyping) of these cell lines serves to enhance their utility in future studies aimed at gene discovery and gene function.
Karpova
Maria B
MB
Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, S-171 76 Stockholm, Sweden.
Schoumans
Jacqueline
J
Blennow
Elisabeth
E
Ernberg
Ingemar
I
Henter
Jan-Inge
JI
Smirnov
Aleksandr F
AF
Nordenskjöld
Magnus
M
Fadeel
Bengt
B
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D019457:Chromosome Breakage / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D032681:Spectral Karyotyping; D014178:Translocation, Genetic
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D005047:Etoposide