Washington: Researchers have identified a group of proteins that are mutated in about one-fifth of all human cancers and may play a key role in preventing tumours.
The finding at the Stanford University School of Medicine suggests that the proteins, which are members of a protein complex that affects how DNA is packaged in cells, work to suppress the development of tumours in many types of tissues.
The broad reach of the effect of mutations in the complex, called BAF, rivals that of another well-known tumour suppressor called p53.
“Although we knew that this complex was likely to play a role in preventing cancer, we didn’t realise how extensive it would be,” said postdoctoral scholar Cigall Kadoch.
Chromatin-regulatory complexes work to keep DNA tightly condensed, while also granting temporary access to certain portions for replication or to allow the expression of genes necessary for the growth or function of the cell.
“Somehow these chromatin-regulatory complexes manage to compress nearly two yards of DNA into a nucleus about one one-thousandth the size of a pinhead,” said Gerald Crabtree, MD, professor of developmental biology and of pathology.
“And they do this without compromising the ability of the DNA to be replicated and selectively expressed in different tissues — all without tangling,” said Crabtree.
The importance of the BAF complex as a tumour suppressor is further emphasised by the fact that, in some cases, a mutation in one subunit is sufficient to initiate cancer development.
“For example a type of mutation called a chromosomal translocation in the gene encoding one of these newly identified subunits, SS18, is known to be the hallmark of a cancer called synovial sarcoma. It is clearly the driving oncogenic event and very often the sole genomic abnormality in these cancers,” said Kadoch.
Kadoch used an antibody that recognised one core component to purify intact BAF complexes in various cell types, including embryonic stem cells and skin, nerve and other cells. She then analysed the various proteins isolated by the technique.
Using this method, Kadoch identified seven proteins previously unknown to be BAF components.
The results, once the newly discovered members were included, were surprising: 19.6 per cent of all human tumours displayed a mutation in at least one of the complex’s subunits.
In addition, for some types of cancers (such as synovial sarcoma), every individual tumour sample examined had a mutation in a BAF subunit.
The results suggest that the BAF complex, when unmutated, plays an important protective role against the development of cancer in many different tissues.
