In Vivo Amplification of the PAX3-FKHR and PAX7-FKHR Fusion Genes in Alveolar Rhabdomyosarcoma

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Abstract
In the pediatric cancer alveolar rhabdomyosarcoma, characteristic t(2;13)(q35;q14) or variant t(1,13)(p36;q14) chromosomal translocations generate PAX3-FKHR or PAX7-FKHR fusion genes. Using fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction and quantitative Southern blot analyses, we demonstrate that these fusion genes are amplified in 20% of fusion-positive tumors. In particular, we found in vivo amplification of these fusions in one of 22 PAX3-FKHR-positive cases and five of seven PAX7-FKHR-positive cases. These findings indicate that translocation and amplification can occur sequentially in a cancer to alter both the structure and copy number of a gene and thereby activate oncogenic activity by complementary mechanisms.