Mapping Genes Could Improve Cancer Diagnosis

Large-scale changes to the structure of the genome are often seen in cancer cells and scientists have found a way to detect these changes, which could enhance cancer diagnosis and aid the use of targeted treatments.

Chromosomal rearrangements occur constitutionally in the general population and somatically in the majority of cancers. Detection of balanced rearrangements, such as reciprocal translocations and inversions, is troublesome, which is particularly detrimental in oncology where rearrangements play diagnostic and prognostic roles.

A team of medical scientists led by those at the Babraham Institute (Cambridge, UK) has developed a new application of a technique called Hi-C, which allows scientists to map how genetic material is arranged inside cells. By analyzing this information, investigators can reliably identify major genetic changes that other methods may miss. This all comes at a lower cost than standard DNA sequencing methods.

Hi-C can detect chromosome rearrangements, where large sections of DNA are exchanged or moved between pieces of the genome called chromosomes, and also copy number variation, where genetic material gets copied or deleted. Both of these changes can have drastic effects on how the cell behaves. The team used Hi-C to examine the genome of cancer cells from six people with brain tumors. They were able to identify major genome changes, often with pinpoint accuracy. Uniquely, this approach allows doctors and scientists to study genetic changes in the wider context of the whole genome. Hi-C could become a powerful tool for understanding the complex genetic changes found in many cancers.

The use of Hi-C on the six primary tumor samples revealed amplifications of known oncogenes, deletions of a tumor suppressor gene and many structural rearrangements, both balanced and unbalanced. One balanced rearrangement studied in detail was shown to result in the fusion of two genes known to be involved in cancer. Hi-C does not rely on the presence of dividing cells and can be used on all nucleated cell types. It is therefore a powerful tool in the analysis of solid tumors, where cytogenetic analysis is difficult and rarely performed as part of routine diagnosis/analysis, yet fusion genes can play a critical clinical role. Hi-C allows these tumors to be interrogated and provides a means to alleviate the bias in detection of both chromosomal rearrangements and fusion genes towards blood borne cancers.

Peter Fraser, PhD, a professor and the lead investigator of the study said, “Hi-C could play a pivotal role in the detection of chromosomal abnormalities and may aid the discovery of new fusion genes. The technique works with much lower quality samples than current techniques and has the additional advantage of being able to provide copy number information from the same data. This all comes at a significantly lower cost than standard methods that use DNA sequencing.” The study was published on June 27, 2017, in the journal Genome Biology.

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Babraham Institute