A Quantitative Analysis of Genomic Instability in Lymphoid and Plasma Cell Neoplasms Based on the PIG-A Gene

Overview

Journal Mutat Res

Publisher Elsevier

Specialty Genetics

Date 2010 Jan 12

PMID 20060400

Citations 7

Authors

David J Araten

Jose A Martinez-Climent

Mary Ann Perle

Eliana Holm

Leah Zamechek

Kimberly Ditata

Katie J Sanders

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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PIGN gene expression aberration is associated with genomic instability and leukemic progression in acute myeloid leukemia with myelodysplastic features.

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Both PIGA and PIGL mutations cause GPI-a deficient isolates in the Tk6 cell line.

Nicklas J, Carter E, Albertini R Environ Mol Mutagen. 2015; 56(8):663-73.

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The rate of spontaneous mutations in human myeloid cells.

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References

Keller P, Payne J, Tremml G, Greer P, Gaboli M, Pandolfi P . FES-Cre targets phosphatidylinositol glycan class A (PIGA) inactivation to hematopoietic stem cells in the bone marrow. J Exp Med. 2001; 194(5):581-9. PMC: 2195941. DOI: 10.1084/jem.194.5.581. View

Green M, ONeill J, Cole J . Suggestions concerning the relationship between mutant frequency and mutation rate at the hprt locus in human peripheral T-lymphocytes. Mutat Res. 1995; 334(3):323-39. DOI: 10.1016/0165-1161(95)90070-5. View

Hu R, Mukhina G, Piantadosi S, Barber J, Jones R, Brodsky R . PIG-A mutations in normal hematopoiesis. Blood. 2005; 105(10):3848-54. PMC: 1895084. DOI: 10.1182/blood-2004-04-1472. View

Mestre-Escorihuela C, Rubio-Moscardo F, Richter J, Siebert R, Climent J, Fresquet V . Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas. Blood. 2006; 109(1):271-80. DOI: 10.1182/blood-2006-06-026500. View

Brodsky R, Mukhina G, Nelson K, Lawrence T, Jones R, Buckley J . Resistance of paroxysmal nocturnal hemoglobinuria cells to the glycosylphosphatidylinositol-binding toxin aerolysin. Blood. 1999; 93(5):1749-56. View

Loeb L . Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 1991; 51(12):3075-9. View

Glaab W, Tindall K . Mutation rate at the hprt locus in human cancer cell lines with specific mismatch repair-gene defects. Carcinogenesis. 1997; 18(1):1-8. DOI: 10.1093/carcin/18.1.1. View

Albertini R, Nicklas J, ONeill J, Robison S . In vivo somatic mutations in humans: measurement and analysis. Annu Rev Genet. 1990; 24:305-26. DOI: 10.1146/annurev.ge.24.120190.001513. View

Araten D, Nafa K, Pakdeesuwan K, Luzzatto L . Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc Natl Acad Sci U S A. 1999; 96(9):5209-14. PMC: 21843. DOI: 10.1073/pnas.96.9.5209. View

10.

Kendal W, Frost P . Pitfalls and practice of Luria-Delbrück fluctuation analysis: a review. Cancer Res. 1988; 48(5):1060-5. View

11.

Hillmen P, Bessler M, Mason P, WATKINS W, Luzzatto L . Specific defect in N-acetylglucosamine incorporation in the biosynthesis of the glycosylphosphatidylinositol anchor in cloned cell lines from patients with paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci U S A. 1993; 90(11):5272-6. PMC: 46698. DOI: 10.1073/pnas.90.11.5272. View

12.

Carrel L, Willard H . X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005; 434(7031):400-4. DOI: 10.1038/nature03479. View

13.

Chen R, Eshleman J, Brodsky R, Medof M . Glycophosphatidylinositol-anchored protein deficiency as a marker of mutator phenotypes in cancer. Cancer Res. 2001; 61(2):654-8. View

14.

Lin Y, Perkins J, Zhang Z, Aplan P . Distinct mechanisms lead to HPRT gene mutations in leukemic cells. Genes Chromosomes Cancer. 2004; 39(4):311-23. DOI: 10.1002/gcc.20005. View

15.

Araten D, Golde D, Zhang R, Thaler H, Gargiulo L, Notaro R . A quantitative measurement of the human somatic mutation rate. Cancer Res. 2005; 65(18):8111-7. DOI: 10.1158/0008-5472.CAN-04-1198. View

16.

Araten D, Bessler M, McKenzie S, Castro-Malaspina H, Childs B, Boulad F . Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clones. Leukemia. 2002; 16(11):2243-8. DOI: 10.1038/sj.leu.2402694. View

17.

Hu R, Mukhina G, Lee S, Jones R, Englund P, Brown P . Silencing of genes required for glycosylphosphatidylinositol anchor biosynthesis in Burkitt lymphoma. Exp Hematol. 2009; 37(4):423-434.e2. PMC: 2763298. DOI: 10.1016/j.exphem.2009.01.003. View

18.

Bachl J, Dessing M, Olsson C, VON Borstel R, Steinberg C . An experimental solution for the Luria-Delbrück fluctuation problem in measuring hypermutation rates. Proc Natl Acad Sci U S A. 1999; 96(12):6847-9. PMC: 22004. DOI: 10.1073/pnas.96.12.6847. View

19.

Miyata T, Takeda J, Iida Y, Yamada N, Inoue N, Takahashi M . The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science. 1993; 259(5099):1318-20. DOI: 10.1126/science.7680492. View

20.

Sjoblom T, Jones S, Wood L, Parsons D, Lin J, Barber T . The consensus coding sequences of human breast and colorectal cancers. Science. 2006; 314(5797):268-74. DOI: 10.1126/science.1133427. View