For the correlation between the CGH breakage regions and chromosome fragile sites (CFSs), we used the previously described randomized approach comparing the CGH regions with the aphidicolin-induced CFS region list as presented in Figure S1 of (Fungtammasan et al., 2012 ).
In order to calculate the correlation between the identified CGH breakage regions and transcription, gene start- and end-points were identified using Ensembl GRCh37, and the number of CGH regions that overlapped by at least one base with a gene was calculated.
The TFO-BCL2 binds to the BCL2 gene in close proximity to a known major-breakage-region (mbr).
Due to breakage, the region of the ventral skull posterior to the toothrows is incompletely known.
Firstly, duplicated genes might cause instability and increased rate of DBS [ 71] or might be breakage "permissive" regions [ 70].
By chi-squared analysis the distribution of breakpoints across the different chromosome bands was non-random (p = 0.0001), suggesting that rearrangements of 8p are under selective pressure or that breaks occur non-randomly due to breakage-prone regions.
The question we are interested in is whether breakage of a region at a specific branch (event 1) co-occurs with a breakage of the same region in another branch (event 2) more frequently than one would expect by chance alone.
We found recurrent breakpoint regions in the cell lines and breakage of several regions present in primary ESCC tumors, which may contribute to disruption of critical genes.
We then discuss the hypothesis that regions with an enhanced susceptibility to breakage correspond to regions of high transcriptional activity and replication initiation.
What is evident, however, is that oncogene-induced replication stress leads to DSBs and other chromosomal aberrations preferentially in regions on the chromosomes that are prone to breakage and rearrangements, regions that are called common fragile sites (CFS) (Di Micco et al., 2006; Tsantoulis et al., 2008).
