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A quantitative analysis of genomic instability in lymphoid and plasma cell neoplasms based on thePIG-Agene

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
Publication Date
DOI: 10.1016/j.mrfmmm.2009.11.012
  • Genomic Instability
  • Hypermutability
  • Lymphoid Neoplasms
  • Plasma Cell Neoplasms
  • Pig-Agene
  • Gpi-Linked Proteins
  • Biology
  • Medicine


Abstract It has been proposed that hypermutability is necessary to account for the high frequency of mutations in cancer. However, historically, the mutation rate ( μ) has been difficult to measure directly, and increased cell turnover or selection could provide an alternative explanation. We recently developed an assay for μ using PIG-A as a sentinel gene and estimated that its average value is 10.6 × 10 −7 mutations per cell division in B-lymphoblastoid cell lines (BLCLs) from normal donors. Here we have measured μ in human malignancies and found that it was elevated in cell lines derived from T cell acute lymphoblastic leukemia, mantle cell lymphoma, follicular lymphoma in transformed phase, and 2 plasma cell neoplasms. In contrast, μ was much lower in a marginal zone lymphoma cell line and 5 other plasma cell neoplasms. The highest μ value that we measured, 3286 × 10 −7, is 2 orders of magnitude above the range we have observed in non-malignant human cells. We conclude that the type of genomic instability detected in this assay is a common but not universal feature of hematologic malignancies.

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