Yuri E. Nukiforov led a team of researchers from both Cincinnati University and the University of Munich in identifying a novel oncogene (a mutated and/or overproduced version of a normal gene that alone or together with other changes can convert a cell into a tumor cell) in papillary thyroid carcinomas that developed in patients exposed to radiation at Chernobyl. Their results are published in the January 3 issue of the Journal of Clinical Investigation.

Mutations of the genes BRAF, RET, or RAS are found in 70% of all cases of papillary thyroid tumors. In sporadic tumors (where patients have not been exposed to high levels of radiation), the most common genetic mutational event occurs within the BRAF gene. In contrast, mutations observed in radiation-induced tumors most commonly involve fusion of one end of the RET gene to the opposite end of various other genes to create a "chimeric oncogene." The two most common gene rearrangement types are called RET/PTC1 and RET/PTC3. Both types of mutations promote transformation of normal cells into malignant cells.

In their current study, Nukiforov and colleagues identified a novel oncogene in Chernobyl residents with papillary thyroid cancer. This oncogene resulted from fusion of part of the AKAP9 gene with one end of the BRAF gene; both genes are present within chromosome 7. The intrachromosomal AKAP9-BRAF fusion event resulted in the loss of portions of the BRAF protein that normally inhibit the kinase activity of BRAF. BRAF is then able to transmit uncontrolled signals to normal cells that promote their division and transformation into malignant tumor cells.

In an accompanying commentary, Alfredo Fusco and colleagues from Universit degli Stud
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Contact: Brooke Grindlinger
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Journal of Clinical Investigation
3-Jan-2005