New mechanism for inactivation of genes in cancer cells

Proteins in leukaemia cells were found to be truncated because of molecular mechanism: polyadenylation of introns.

Many genes play antagonistic roles in cancer cells. Broad classification divides them into tumor suppressors (blocking emergence of a cancer) and tumor promoters (supporting emergence of a cancer). Majority of genes acting as tumor suppressors produce protein molecules which govern crucial biochemical pathways. In most types of cancers, those proteins are variously damaged and because of that not serving correctly. One of malfunction types is truncation of a protein.

Researchers have found that in leukaemia common cause of protein truncation is not mutation of a tumor suppressor gene. Instead of that modification, change was present in stages before protein molecule creation. In physiological state, during these stages occur many biochemical reactions which lead from gene to a protein. One of them is called splicing – consists of cutting out fragments of a gene (introns). Leukaemia cells modify intron handling by adding to them new compounds. This addition disturbs normal protein production and further allows cancer to emerge and grow.

More: “Widespread intronic polyadenylation inactivates tumour suppressor genes in leukaemia”, S. Lee et al., 2018, doi:10.1038/s41586-018-0465-8