title: Dominant expansion of a cryptic subclone with an abnormal karyotype in B lymphoblastoid cell lines during culture.
abstract: Although B lymphoblastoid cell lines (B-LCLs) are thought to maintain their original genomic structures during long-term culture, there has been considerable disagreement on the actual genomic stability of these cells. This study was initiated to determine whether B-LCLs develop cell populations with abnormal genomes during culture and to search for factors important to the maintenance of the original genome. We established continuous cultures of B-LCLs for more than 6 months and analyzed the cells using array-based comparative genome hybridization (CGH) analysis, conventional karyotyping and analysis of V(D)J recombination in the immunoglobulin (Ig) gene. We found that one B-LCL acquired an extra chromosome 4 without any other genomic rearrangements at passage 16 of continuous culture. At the Ig light- and heavy-chain loci, analysis of the major cell population showed a difference between cultures at early and later passages. Another aneuploid line was detected among B-LCLs established elsewhere and deposited previously into the RIKEN Cell Bank. Our findings indicate that some of the genomic rearrangements in B-LCLs are not caused by gradual accumulation of mutations and rearrangements during the B-LCL establishment processes, but rather as a result of a change in the cell population from clones with a normal genome to clones with de novo rearrangements. It is therefore feasible to maintain B-LCLs with a normal genomic structure by cell cloning or similar treatment.
authors.affiliation: Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Danjoh
authors.forename: R
authors.initials: R
authors.lastname: Shirota
authors.forename: T
authors.initials: T
authors.lastname: Hiroyama
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D059786:Abnormal Karyotype; D000328:Adult; D000782:Aneuploidy; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D055028:Comparative Genomic Hybridization; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D059785:Karyotype; D013997:Time Factors; D060152:V(D)J Recombination