Non-random chromosomal translocations are frequently associated with a variety of cancers, particularly hematologic malignancies and childhood sarcomas.

Chromosome aberrations, in particular translocations and their corresponding gene fusions, have an important role in the initial steps of tumorigenesis.

 List of tumoral translocations

Physiopathology

 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.

 Mutations in DNA-repair pathways have been implicated in the production of chromosomal translocations in humans, mice and yeast.

 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.

 Oncogenic chromosomal translocation partners can be identified by proteomic methods (16651537)

Gene fusions

In most tumors with acquired chromosomal translocations, a new fusion oncogene or promoter-oncogene fusion is created and drives tumor growth. In 2007, 358 gene fusions involving 337 different genes have been identified.

An increasing number of gene fusions are being recognized as important diagnostic and prognostic parameters in malignant haematological disorders and childhood sarcomas.

The biological and clinical impact of gene fusions in the more common solid tumour types has been less appreciated.

However, an analysis of available data shows that gene fusions occur in all malignancies, and that they account for 20% of human cancer morbidity.

Gene deletions

Some translocations drive tumorigenesis via deletion of a tumor suppressor, as t(X;18) in Wilms tumor (17620295)

See also

 amplification of fusion genes
 fusion transcripts
 fusion proteins
 tumoral translocations

 translocation-associated proliferations

• translocation-associated leukemias
• translocation-associated tumors
  • translocation-associated Lymphomas
  • translocation-associated sarcomas
  • translocation-associated carcinomas

 chromosomal translocations
 Oncobase

Reviews

 Rabbitts TH. Chromosomal translocations in human cancer. Nature 1994;372:143-149. PMID: 7969446

 Rowley JD. The critical role of chromosome translocations in human leukemias. Annu Rev Genet 1998;32:495-519. PMID: 9928489

 Meyerson M. Cancer: broken genes in solid tumours. Nature 2007;448:545-546. PMID: 17671492

 Shaffer DR, Pandolfi PP. Breaking the rules of cancer. Nat Med 2006;12:14-15. PMID: 16397543

 Greaves MF, Wiemels J. Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer 2003;3:639-649. PMID: 12951583

 Mitelman F, Johansson B, Mertens F. The impact of translocations and gene fusions on cancer causation. Nat Rev Cancer. 2007 Apr;7(4):233-45. PMID: 17361217

 Novo FJ, Vizmanos JL. Chromosome translocations in cancer: computational evidence for the random generation of double-strand breaks. Trends Genet. 2006 Apr;22(4):193-6. PMID: 16499992

 Elenitoba-Johnson KS, Crockett DK, Schumacher JA, Jenson SD, Coffin CM, Rockwood AL, Lim MS. Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase fusion proteins. Proc Natl Acad Sci U S A. 2006 May 9;103(19):7402-7. PMID: 16651537

 Rabbitts TH, Stocks MR. Chromosomal translocation products engender new intracellular therapeutic technologies. Nat Med. 2003 Apr;9(4):383-6. PMID: 12669051

 Aplan PD. Causes of oncogenic chromosomal translocation. Trends Genet. 2006 Jan;22(1):46-55. PMID: 16257470

 Greaves MF, Wiemels J. Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer. 2003 Sep;3(9):639-49. PMID: 12951583

 Rego EM, Pandolfi PP. Reciprocal products of chromosomal translocations in human cancer pathogenesis: key players or innocent bystanders? Trends Mol Med. 2002 Aug;8(8):396-405. PMID: 12127726

 Tomescu O, Barr FG. Chromosomal translocations in sarcomas: prospects for therapy. Trends Mol Med. 2001 Dec;7(12):554-9. PMID: 11733218

References

 Han M, Rivera MN, Batten JM, Haber DA, Cin PD, Iafrate AJ. Wilms? tumor with an apparently balanced translocation t(X;18) resulting in deletion of the WTX gene. Genes Chromosomes Cancer. 2007 Oct;46(10):909-13. PMID: 17620295

 Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960;25:85-109. PMID: 14427847