Barr F G, Nauta L E, Davis R J, Schäfer B W, Nycum L M, Biegel J A
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Hum Mol Genet. 1996 Jan;5(1):15-21. doi: 10.1093/hmg/5.1.15.
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.
在儿童癌症肺泡横纹肌肉瘤中，特征性的t(2;13)(q35;q14)或变异的t(1;13)(p36;q14)染色体易位产生PAX3-FKHR或PAX7-FKHR融合基因。通过荧光原位杂交、逆转录聚合酶链反应和定量Southern印迹分析，我们证明这些融合基因在20%的融合阳性肿瘤中发生扩增。特别是，我们在22例PAX3-FKHR阳性病例中的1例以及7例PAX7-FKHR阳性病例中的5例中发现了这些融合基因的体内扩增。这些发现表明，在癌症中易位和扩增可能依次发生，从而改变基因的结构和拷贝数，进而通过互补机制激活致癌活性。
