Scientists in the U.K. report that cancer manipulates a natural cell process to promote its survival. Controlling this mechanism may halt progress of the disease, the investigators say.
Their study (“A Pan-Cancer Genome-Wide Analysis Reveals Tumour Dependencies by Induction of Nonsense-Mediated Decay”) is published in Nature Communications.
“We discover cancer-specific NMD [nonsense mediated decay]-elicit signatures in TSGs [tumor suppressor genes] and cancer-associated genes,” write the researchers. “Our analysis reveals a previously unrecognized dependence of hypermutated tumors on hypofunction of genes that are involved in chromatin remodeling and translation.”
NMD is a natural physiological process that allows cells to detect nonsense mutations. It also enables these cells to remove the mutated message (decay) that comes from these faulty genes before they can be translated into proteins that can cause disease formation.
NMD is known for the role it plays in the development of genetic diseases, such as cystic fibrosis, and some hereditary forms of cancer. But not all nonsense mutations can elicit NMD; so until now, its wider impact on cancer was largely unknown, point out the researchers.
A team from the University of Oxford Medical Sciences Division and the University of Birmingham developed a computer algorithm to mine DNA sequences from cancer to accurately predict whether or not an NMD would eliminate genes that had nonsense mutations. The work originally focused on ovarian cancer and found that about a fifth of these cancers use NMD to become…