Given that frequent breakpoints coincide with the position of ESAG3 loci between linkage blocks, these could play a role in orientating expression sites prior to the exchange of intervening regions.
In a relatively small sample size enriched for high-risk breast cancers, we observed frequent breakpoints patterns and configurations of DNA breaks suggestive of chromothripsis, a recently reported phenomenon of genomic catastrophe affecting various chromosomes [ 5, 6].
The ZNF331 gene lies close to a frequent breakpoint region of follicular thyroid adenomas (Meiboom et al. 2003), but the question of why benzene should so markedly affect ZNF331 expression remains unclear at present.
Notably, the most frequent deletion breakpoints, including those of the "common deletion", are bounded by 2G QFP sequence motifs.
In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage.
Our major goal was to define the most frequent recurrent breakpoint regions in metastatic CRC and the commonly gained and/or deleted genes in the altered chromosomes.
Apart from defining the most frequently altered genes in metastatic CRC, this study was also aimed at detailed characterization of the most frequent recurrent breakpoint regions associated with such genetic changes.
Because the variant ARID5B rs10821936 allele was remarkably associated with an increased risk of MLL-r acute leukemia, we tested whether this risk allele was associated to a specific MLL TPG or to any of the frequent MLL breakpoint regions.
It therefore seems that some breast carcinomas of luminal A and luminal B phenotypes, showing important genetic instability with a large number of DNA breakpoints, frequent TP53 mutations, and frequent gene amplification are characterized by very poor outcome.
Moreover, studies by Courtay-Cahen et al (2000), as well as our work (Adélaïde et al, 2003, and data not shown), have suggested the frequent presence of breakpoints located centromeric to NRG1 (Gelsi-Boyer et al, in preparation).
Interestingly, however, one sample (MM4) showed frequent genomic breaks (133 breakpoints) with higher methylation levels at the breakpoints.
