Loss of the tumour suppressor protein TET2 can pave the way for gene mutations that drive myeloid, lymphoid and other cancers, researchers say.
TET2 helps prevent haematopoietic stem cells from overgrowing, but becomes ineffective if it is mutated, allowing other genes to mutate. An estimated 5% of people over the age of 70 have TET2 mutations.
Dr Mingjiang Xu of the University of Miami, USA, and colleagues have found that loss of TET2 is unique in that it plays a role in several blood cancers, rather than just a specific type of cancer, as is the case for many mutated genes.
Dr Xu says: 'If you lose TET2, it's not a malignant state, per se, but it's creating a situation for other mutations to happen, leading to all types of blood cancer.'
For example, TET2 mutations are found in 30% of myelodysplastic syndrome cases, 30% of secondary acute myeloid leukaemias and more than 50% of chronic myelomonocytic leukaemias.
He continues: 'We are developing a method to target TET2. If we target that population for early therapy, we could potentially prevent those downstream mutations from happening.'
In lab tests, the team confirmed that TET2 demethylates DNA, operating as a 'master switch' that controls whether certain genes are turned on or off. They show that mice without the TET2 gene are at a raised risk of blood cancers.
Their new findings were published in Nature Communications.
In terms of boosting TET2, therapeutic options are limited and any intervention must happen early in the process before several mutations are acquired, the researchers say.
Source: Pan, F. et al. Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells. Nature Communications 25 April 2017 doi: 10.1038/ncomms15102
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