Two-faced gene shifts the paradigm of cancer mutation studies

Oesophageal adenocarcinoma is the fallout of a condition called Barrett’s oesophagus (BO) which is marked by a cancer-causing abnormality of cells lining the oesophagus. Survival for oesophageal cancer is a formidable challenge as it is often diagnosed at advanced stages.

Research teams from Francis Crick Institute and Barts Cancer Institute sought to understand why only a mere 1% of BO patients develop cancer. The team found that loss of both CDKN2A and p53 (another key gene and a critical tumour suppressor) tend to weaken potentially cancerous cells. Since they can’t compete with normal cells around them, cancer doesn’t take root. Conversely, if cancer cells lose CDKN2A after the disease has had time to develop, cancer forms and turns aggressive culminating in worse outcomes for patients.

This breakthrough research has shown how the context is extremely important in the study of mutations in cancer genes. The researchers have aptly likened the dual role of CDKN2A to the ancient Roman god of transitions Janus, after whom the month January gets its name. Janus has two faces – one looking to the past and one to the future. Likwise, CDKN2A plays a twin role: one undesirable and the other beneficial.

Although further probe is imperative for fool-proof validation, this seminal discovery, going forward it can help doctors quickly identify individuals at a greater risk of developing cancer, thereby leading to more effective and personalised therapies and strategies.

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