Causes of Oncogenic Chromosomal Translocation

Overview

Journal Trends Genet

Specialty Genetics

Date 2005 Nov 1

PMID 16257470

Citations 83

Authors

Peter D Aplan

Affiliations

Soon will be listed here.

Abstract

Non-random chromosomal translocations are frequently associated with a variety of cancers, particularly hematologic malignancies and childhood sarcomas. In addition to their diagnostic utility, chromosomal translocations are increasingly being used in the clinic to guide therapeutic decisions. However, the mechanisms that cause these translocations remain poorly understood. Illegitimate V(D)J recombination, class switch recombination, homologous recombination, non-homologous end-joining and genome fragile sites all have potential roles in the production of non-random chromosomal translocations. In addition, mutations in DNA-repair pathways have been implicated in the production of chromosomal translocations in humans, mice and yeast. Although initially surprising, the identification of these same oncogenic chromosomal translocations in peripheral blood from healthy individuals strongly suggests that the translocation is not sufficient to induce malignant transformation, and that complementary mutations are required to produce a frank malignancy.

Citing Articles

RUNX1/NPM1/H3K4me3 complex contributes to extracellular matrix remodeling via enhancing FOSL2 transcriptional activation in glioblastoma.

Cui X, Huo D, Wang Q, Wang Y, Liu X, Zhao K Cell Death Dis. 2024; 15(1):98.

PMID: 38286983 PMC: 10825180. DOI: 10.1038/s41419-024-06481-4.

Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement.

Gray Z, Chakraborty D, Duttweiler R, Alekbaeva G, Murphy S, Chetal K Cell. 2023; 186(21):4528-4545.e18.

PMID: 37788669 PMC: 10591855. DOI: 10.1016/j.cell.2023.09.009.

Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment.

Burmeister T, Groger D, Gokbuget N, Spriewald B, Starck M, Elmaagacli A Sci Rep. 2023; 13(1):15167.

PMID: 37704696 PMC: 10499895. DOI: 10.1038/s41598-023-42294-9.

Structure and mechanism in non-homologous end joining.

Vogt A, He Y DNA Repair (Amst). 2023; 130:103547.

PMID: 37556875 PMC: 10528545. DOI: 10.1016/j.dnarep.2023.103547.

Mechanisms of insertions at a DNA double-strand break.

Min J, Zhao J, Zagelbaum J, Lee J, Takahashi S, Cummings P Mol Cell. 2023; 83(14):2434-2448.e7.

PMID: 37402370 PMC: 10527084. DOI: 10.1016/j.molcel.2023.06.016.

References

Roix J, McQueen P, Munson P, Parada L, Misteli T . Spatial proximity of translocation-prone gene loci in human lymphomas. Nat Genet. 2003; 34(3):287-91. DOI: 10.1038/ng1177. View

Mills K, Ferguson D, Alt F . The role of DNA breaks in genomic instability and tumorigenesis. Immunol Rev. 2003; 194:77-95. DOI: 10.1034/j.1600-065x.2003.00060.x. View

Bassing C, Suh H, Ferguson D, Chua K, Manis J, Eckersdorff M . Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell. 2003; 114(3):359-70. DOI: 10.1016/s0092-8674(03)00566-x. View

Celeste A, Difilippantonio S, Difilippantonio M, Fernandez-Capetillo O, Pilch D, Sedelnikova O . H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell. 2003; 114(3):371-383. PMC: 4737479. DOI: 10.1016/s0092-8674(03)00567-1. View

Helman L, Meltzer P . Mechanisms of sarcoma development. Nat Rev Cancer. 2003; 3(9):685-94. DOI: 10.1038/nrc1168. View

Reddien P, Cameron S, Horvitz H . Phagocytosis promotes programmed cell death in C. elegans. Nature. 2001; 412(6843):198-202. DOI: 10.1038/35084096. View

Hoeppner D, Hengartner M, Schnabel R . Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans. Nature. 2001; 412(6843):202-6. DOI: 10.1038/35084103. View

Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti R, Kuppers R . Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature. 2001; 412(6844):341-6. DOI: 10.1038/35085588. View

Bergsagel P, Kuehl W . Chromosome translocations in multiple myeloma. Oncogene. 2001; 20(40):5611-22. DOI: 10.1038/sj.onc.1204641. View

10.

Rabbitts T . Chromosomal translocation master genes, mouse models and experimental therapeutics. Oncogene. 2001; 20(40):5763-77. DOI: 10.1038/sj.onc.1204597. View

11.

Stanulla M, Chhalliyil P, Wang J, Aplan P . Mechanisms of MLL gene rearrangement: site-specific DNA cleavage within the breakpoint cluster region is independent of chromosomal context. Hum Mol Genet. 2001; 10(22):2481-91. DOI: 10.1093/hmg/10.22.2481. View

12.

Rowley J . Chromosome translocations: dangerous liaisons revisited. Nat Rev Cancer. 2002; 1(3):245-50. DOI: 10.1038/35106108. View

13.

Elliott B, Jasin M . Double-strand breaks and translocations in cancer. Cell Mol Life Sci. 2002; 59(2):373-85. PMC: 11146114. DOI: 10.1007/s00018-002-8429-3. View

14.

Slovak M, Bedell V, Popplewell L, Arber D, Schoch C, Slater R . 21q22 balanced chromosome aberrations in therapy-related hematopoietic disorders: report from an international workshop. Genes Chromosomes Cancer. 2002; 33(4):379-94. DOI: 10.1002/gcc.10042. View

15.

Block A, Carroll A, Hagemeijer A, Michaux L, van Lom K, Olney H . Rare recurring balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop. Genes Chromosomes Cancer. 2002; 33(4):401-12. DOI: 10.1002/gcc.10044. View

16.

Olney H, Mitelman F, Johansson B, Mrozek K, Berger R, Rowley J . Unique balanced chromosome abnormalities in treatment-related myelodysplastic syndromes and acute myeloid leukemia: report from an international workshop. Genes Chromosomes Cancer. 2002; 33(4):413-23. DOI: 10.1002/gcc.10045. View

17.

Myung K, Kolodner R . Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2002; 99(7):4500-7. PMC: 123677. DOI: 10.1073/pnas.062702199. View

18.

Wang J . Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol. 2002; 3(6):430-40. DOI: 10.1038/nrm831. View

19.

Mori H, Colman S, Xiao Z, Ford A, Healy L, Donaldson C . Chromosome translocations and covert leukemic clones are generated during normal fetal development. Proc Natl Acad Sci U S A. 2002; 99(12):8242-7. PMC: 123052. DOI: 10.1073/pnas.112218799. View

20.

Gilliland D, Tallman M . Focus on acute leukemias. Cancer Cell. 2002; 1(5):417-20. DOI: 10.1016/s1535-6108(02)00081-8. View