A quantitative analysis of genomic instability in lymphoid and plasma cell neoplasms based on the PIG-A gene.
It has been proposed that hypermutability is necessary to account for the high frequency of mutations in cancer. However, historically, the mutation rate (mu) has been difficult to measure directly, and increased cell turnover or selection could provide an alternative explanation. We recently developed an assay for mu using PIG-A as a sentinel gene and estimated that its average value is 10.6 x 10(-7) mutations per cell division in B-lymphoblastoid cell lines (BLCLs) from normal donors. Here we have measured mu 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, mu was much lower in a marginal zone lymphoma cell line and 5 other plasma cell neoplasms. The highest mu value that we measured, 3286 x 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.
Araten
David J
DJ
Division of Hematology, NYU School of Medicine, NYU Langone Cancer Center, NY, USA. David.Araten@nyumc.org
Martinez-Climent
Jose A
JA
Perle
Mary Ann
MA
Holm
Eliana
E
Zamechek
Leah
L
DiTata
Kimberly
K
Sanders
Katie J
KJ
D045744:Cell Line, Tumor; D002999:Clone Cells; D005434:Flow Cytometry; D042822:Genomic Instability; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D054219:Neoplasms, Plasma Cell / Q000235:genetics*
D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein