Abstract
Kasumi-1 has played an important role in an experimental model with t(8;21) translocation, which is a representative example of leukemia cell lines. However, previous studies using Kasumi-1 show discrepancies in the genome profile. The wide use of leukemia cell lines is limited to lines that are well-characterized. The use of additional cell lines extends research to various types of leukemia, and to further explore leukemia pathogenesis, which can be achieved by uncovering the fundamental features of each cell line with accurate data. In this study, ten Kasumi cell lines established in Japan, including five that were previously unknown, have been characterized by SNP microarray and targeted sequencing. SNP genotyping suggested that the genetic ancestry in four of the ten Kasumi cell lines was not classified as Japanese but covered several different east-Asian ethnicities, suggesting that patients in Japan are genetically diverse. TP53 mutations were detected in two cell lines with complex array profiles, indicating chromosomal instability (CIN). A quantitative assessment of tumor genomes at the chromosomal level was newly introduced to reveal total DNA sizes and Scales of Genomic Alterations (SGA) for each cell line. Kasumi-1 and 6 derived from relapsed phases demonstrated high levels of SGA, implying that the level of SGA would reflect on the tumor progression and could serve as an index of CIN. Our results extend the leukemia cellular resources with an additional five cell lines and provide reference genome data with ethnic identities for the ten Kasumi cell lines.
Highlights
Leukemia genomes are primarily characterized by abnormal karyotypes, which often include the formation of a fusion gene [1]
Analysis of MCF7 strains revealed genetic evolution of cancer cell lines during cell culture [18]. This implies that tumor genomes change during in vitro cell culture, which can be explained by an in vitro clonal evolution model [19]
Mutation analysis by target sequencing was conducted using a multiplex panel, OncomineTM Myeloid Research Assay (Thermo Fisher Scientific, A36941), consisting of 40 DNA genes analyzed by 526 amplicons and 29 RNA genes representing 700 fusion isoforms found in major myeloid disorders
Summary
Leukemia genomes are primarily characterized by abnormal karyotypes, which often include the formation of a fusion gene [1]. Recurrent hotspot mutations have been identified in association with leukemogenesis [5] Both large-scale changes at chromosome level and nucleotide changes at sequence level contribute to a diverse array of leukemia genomes, reflecting a broad range of subtypes [6, 7]. Kasumi leukemia cell lines: characterization of tumor genomes with ethnic origin and scales. They were named after the location of the laboratory in the Kasumi area of Hiroshima city [8] (Table 1). Analysis of MCF7 strains revealed genetic evolution of cancer cell lines during cell culture [18] This implies that tumor genomes change during in vitro cell culture, which can be explained by an in vitro clonal evolution model [19]. Our study demonstrates quantitative assessment of leukemia genomes and adds ethnic information on each cell line
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