Recurrent chromosomal translocations: Is proximity a rule?

Abstract

The role of recurrent chromosomal translocations in pathogenesis is well characterized in many leukemia subtypes; however, the factors leading to such preferential gene fusions are yet to be understood. The proximity of the genetic regions is considered important for genetic exchange, and interphase molecular cytogenetic methods can be employed to measure the same. The interphase genomic location of gene pairs taking part in translocations which are non-randomly associated with leukemia subtypes was studied for the extent of proximity by measuring relative distance and radial location. The FISH (Fluorescence In Situ Hybridization) signals corresponding to gene pairs were scored for relative distance and percentage of possible translocation pairs showing proximity which was found higher for BCR-ABL, PML-RARA and AML-ETO. The radial position of the gene pairs was also recorded to see if there is any preferred location in terms of nuclear centre or periphery for translocation partners. The results suggested no preferential location of any of the gene pairs in periphery or centre of the interphase nucleus, rather random distribution was observed for all the three cases. We report here the use of simple interphase FISH method to assess the interphase proximity of gene fusion pairs which can be further employed for other translocations.