Hi-C As A New Tool For Precise Detection And Characterization Of Chromosomal Rearrangements And Copy Number Variation In Human Tumors

Chromosomal rearrangements are prevalent events in the human population, occurring both constitutionally in the general population and somatically in the majority of cancers. Detection of balanced rearrangements, such as reciprocal translocations and inversions, is troublesome with many rearrangements remaining undetected. This is particularly detrimental in oncology where rearrangements play diagnostic and prognostic roles and can influence choice and efficacy of treatment protocols. New methods to detect and characterize balanced rearrangements are therefore required for both research and clinical applications. Here we describe the use of the chromosome conformation capture derived method Hi-C as a tool for detection of both balanced and unbalanced chromosomal rearrangements in cell lines and human tumor samples, with the ability to detect gene fusions and define chromosomal breakpoints to base pair resolution. In addition, we show that copy number information can also be obtained from the same data, allowing rearrangements, gains, amplifications and deletions of genomic regions to be detected in a single experiment. Overall design: Performed Hi-C on two human lymphoblastoid cell lines with known chromosomal translocations (FY1199 and DD1618) and on a transformed mouse cell line (EKLF). In addition, performed Hi-C on six human brain tumours: five glioblastomas ( GB176, GB180, GB182, GB183 and GB238) and one anaplastic astrocytoma (AA86). Hi-C was also performed in a human cell line control (GM07017). QDNAseq was performed on the AA86, GB176, GB180, GB182, GB183 and GB238 sampes.