Oncogenic Fusion Disguise

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Science  28 Nov 2008:
Vol. 322, Issue 5906, pp. 1305
DOI: 10.1126/science.322.5906.1305c

Human solid tumors typically display a vast array of genetic alterations, many of which are likely to be secondary events in tumor development rather than the primary drivers of tumor growth. One goal of cancer genomics research is to identify the alterations that cause tumorigenesis and occur at high frequency in a given tumor type, as these alterations are likely to be the most informative ones with respect to the biology of the tumor as well as being the most useful ones for diagnosis and therapy. This principle is illustrated most famously by the oncogenic fusion of the BCR and ABL genes in chronic myelogenous leukemia, the discovery of which ultimately led to successful therapy. To date, however, oncogenic fusion genes have been detected only at low frequency in solid tumors that are common in the general population. Jones et al. suggest that this may be a problem of detection. In a study of pilocytic astrocytomas (a common low-grade brain tumor in children), they found that 29 of 44 tumors harbored a genetic alteration that fused the BRAF oncogene with an uncharacterized gene called KIAA1549. The fusion gene, which was not found in other types of brain tumors, produces a protein with constitutively active BRAF kinase activity and confers tumorigenic potential on NIH-3T3 cells. This gene rearrangement was initially detected as a tandem duplication at 7q34, raising the possibility that similar duplications seen elsewhere in the cancer genome may likewise mark the sites of bona fide oncogenic fusion genes. — PAK

Cancer Res. 68, 8673 (2008).

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