Chromosomal translocations in cancer and their relevance for therapy.
OBJECTIVE
Recurring chromosomal abnormalities are considered the primary genetic change in oncogenesis as well as an important indicator for tumor phenotype and clinical outcome. This review highlights recent findings regarding the genes associated with chromosomal translocations.


RESULTS
A great number of novel fusion genes associated with chromosomal translocations have been cloned. These novel fusion genes are found in the smaller part of various malignancies, and it can be expected that the significance of novel fusion gene occurrence for oncogenesis will be clarified in the not too distant future. Observation of high frequencies of mutations in NOTCH1, NPM and JAK2 in T-cell acute lymphoblastic leukemia, acute myeloid leukemia with normal karyotype and myeloproliferative disorders (polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis) have provided important suggestions for a better understanding of chromosomal translocations. This is because all these genes had already been identified as genes associated with chromosomal translocations in a small subset of specific phenotypes of hematologic malignancies.


CONCLUSIONS
This review summarizes recent findings associated with chromosomal translocations including newly identified fusion genes, a novel mechanism of fusion gene formation and their relevance for novel targeted therapies. Continuing attempts to identify genes associated with chromosomal translocations can be expected to provide further insights into the significance of various gene alterations in cancer and the development of novel targeted therapies.
Taki
Tomohiko
T
Department of Molecular Laboratory Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
Taniwaki
Masafumi
M
D000970:Antineoplastic Agents / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases