Lymphoma is the fifth most common type of cancer in the UK. It is a blood cancer that begins in infection-fighting white blood cells of the immune system called lymphocytes where mutations cause the cells to change into lymphoma cells and grow uncontrollably. To be able to devise new treatments for lymphoma and share more accurate prognoses with patients, it is crucial that we know which mutations cause these changes.
Research published on 4 February in the journal Mobile DNA from our Cancer Genomics group have reported a technical development that will take us one step closer to this aim. The team used a model of lymphoma where mutations are caused by random integrations of virus genomes into the cell’s DNA. To study this model better, they developed a method that accurately measures the abundance of mutations within these tumours, which means that the method quantitates whether mutations are present in the entire tumour, part of the tumour or even in as little as one cell.
This tool will help us to understand which mutations happen earlier in this model system of cancer and which occur at a later stage of the cancer’s evolution. If a mutation is present only in a small proportion of a tumour, then it happened later in the progression of the disease after most of the cell division and growth have occurred. Conversely, mutations found in most cells are likely to be the earliest events in tumour formation.
From a treatment perspective, understanding the abundance of mutations can aid predictions of treatment response. When cancers are treated with various drugs some cells can survive. Knowing which drug resistance mutations those cells had prior to treatment can inform whether a patient might make a full recovery or experience a treatment-resistant relapse.
Anthony Uren, Head of the Cancer Genomics group at the MRC LMS, discussed the next steps for this research:
“We and others can now use this technique to analyse similar tumours to decipher the order of mutations. We want to try and understand why some occur earlier in the disease and some later, and also why some mutations occur in a limited subset of tumours, whereas others occur across a broad spectrum of diverse tumours.”
New insights into how cancers progress benefit from development of this new tool to accurately measure these mutations in cancer cells.
‘LUMI-PCR: an Illumina platform ligation-mediated PCR protocol for integration site cloning, provides molecular quantitation of integration sites’ was published on 4 February in Mobile DNA. Read the full article here.
