A new method to take the DNA fingerprint of individual cancer cells is uncovering the true extent of cancer's genetic diversity, new research reveals.
The technique can identify the founding mutations from which a tumour evolved and then uses computer software to draw a map of the cancer's family tree.
Scientists at The Institute of Cancer Research, London, and the Wellcome Trust Sanger Institute used DNA sequencing to identify a panel of mutations present across thousands of cancer cells in three patients with leukaemia. They then tested hundreds of individual cancer cells for each of the mutations to determine their genetic fingerprint and place them into cancer's family tree.
The study found that each patient's cancer had a distinct family tree, with a unique series of mutations driving their growth.
The findings could be used to identify the key mutations that occur early in the development of tumours, allowing doctors to use targeted treatments more effectively.
The study, published in the journal Genome Research, was funded by Leukaemia and Lymphoma Research, the Kay Kendall Leukaemia Fund, The Institute of Cancer Research (ICR), and the Wellcome Trust.
Tumours grow through a process of Darwinian evolution, where cancer cells develop an advantageous mutation that allows them to survive and multiply, producing a population of cells which can mutate further.
Sequencing the whole genome of a cancer provides a tally of the many mutations that accumulate within it, but can fail to identify where mutations have branched off the evolutionary tree to produce distinct sub-populations of cells.
Targeted cancer treatments are designed to attack molecules produced by mutations, but if the targeted mutation occurs on an evolutionary branch and not the trunk, the treatment will fail as other branches dominate and treatment resistant cells spread.
The new technique used software to assign the cancer cell with the fewest mutations as the ancestral clone and place it at the root of the evolutionary family tree, with the other clones arranged as branches above it.
- N. E. Potter, L. Ermini, E. Papaemmanuil, G. Cazzaniga, G. Vijayaraghavan, I. Titley, A. Ford, P. Campbell, L. Kearney, M. Greaves. Single-cell mutational profiling and clonal phylogeny in cancer. Genome Research, 2013; DOI: 10.1101/gr.159913.113
Cite This Page: