Fusion genes and chromosome translocations in the common epithelial cancers

It has been known for 25 years that fusion genes play a central role in leukaemias and sarcomas but they have been neglected in the common carcinomas, largely because of technical limitations of cytogenetics. In the last few years it has emerged that gene fusions, caused by chromosome translocations...

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Bibliographic Details
Published in:The Journal of pathology 2010-01, Vol.220 (2), p.244-254
Main Author: Edwards, Paul AW
Format: Article
Language:English
Subjects:
Carcinoma
chromosome
Chromosome deletion
Chromosome translocations
epithelia
ETS protein
fusion gene
Gene deletion
Gene fusion
Gene Fusion - genetics
Genes, Neoplasm - genetics
Genome-Wide Association Study
Humans
Inversion
Leukemia
Lung carcinoma
Mutation
neoplasia
Neoplasms, Glandular and Epithelial - genetics
Oligonucleotide Array Sequence Analysis - methods
Promoters
Prostate cancer
Sarcoma
Transcription factors
translocation
Translocation, Genetic - genetics
Tumors
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Summary:It has been known for 25 years that fusion genes play a central role in leukaemias and sarcomas but they have been neglected in the common carcinomas, largely because of technical limitations of cytogenetics. In the last few years it has emerged that gene fusions, caused by chromosome translocations, inversions, deletions, etc., are important in the common epithelial cancers, such as prostate and lung carcinoma. Most prostate cancers, for example, have an androgen-regulated fusion of one of the ETS transcription factor gene family. Early results of genome-wide searches for gene fusions in breast and other epithelial cancers suggest that most individual tumours will have several fused genes. Fusion genes are exceptionally powerful mutations. In their simplest form they can turn on expression by promoter insertion but they can also, for example, force dimerization of a protein or change its subcellular location. They are correspondingly important clinically, in classification and management and as targets for therapy. This review surveys what we know of fusion genes in the carcinomas, summarizes the technical advances that now make it possible to search systematically for such genes, and concludes by putting fusion genes into the current picture of mutation in cancers. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.2632