LAUSR

Somatic structural genome alterations such as changes in copy number or chromosomal rearrangements can promote genome instability and cancer development, and identification of these mutations is crucial to diagnose cancer early and provide targeted therapies. Now, Harewood et al. report the use of Hi-C (a high-throughput derivative of the chromosome conformation capture (3C) technology) for the detection of both balanced and unbalanced chromosomal rearrangements in primary human tumour samples. The same data can also be used to determine copy number profiles. The detection of somatic structural genome alterations in cancer has enormously increased in efficiency and resolution with the development of next-generation sequencing technologies. However, mapping rearrangements in repetitive regions or detecting balanced rearrangements (where the genomic rearrangement does not lead to an overall loss or gain of genetic material), such as reciprocal translocations and inversions, has remained challenging. The authors generated in-nucleus Hi-C heat maps for two human lymphoblastoid cell lines with known chromosomal translocations between chromosomes 11 and 22. Distinct blocks visible on the heat map reflect unusually strong ‘long-range’ cis or trans interactions, which arise when chromosomal rearrangements bring together distal regions of the same or different chromosomes, respectively. The first heat map for a cell line containing an unbalanced rearrangement (where there is either loss or gain of genetic material) showed one distinct block that mapped to known breakpoints. By contrast, a second cell line containing a balanced rearrangement showed two blocks that were joined at the point of strongest contacts, corresponding to known chromosomal breakpoints, which is indicative of a reciprocal translocation. C A N C E R G E N E T I C S