The scientists, based at the University of Dundee – part of an international collaboration reaching from Singapore to California – examined the DNA of more than 60 people with multiple self-healing squamous epithelioma (MSSE) and 110 of their unaffected relatives. They discovered that the disease was caused by faults in a gene called TGFBR1.
The TGFBR1 gene makes a receptor protein through which healthy cells receive messages from their neighbours, instructing them to carry out jobs essential to growth and development.
But cells from a range of cancer types interpret the ‘instructions’ transmitted by TGFBR1 in two completely different ways, depending on the maturity of the tumour.
TGFBR1 initially acts as a ‘brake’ preventing the growth of early tumours of various types. But when cancers become more advanced and aggressive, their cells undergo a ‘signalling switch’. Cancer cells interpret the same messages from TGFBR1 differently. In more advanced cancers, TGFBR1 promotes tumour growth and spread instead.
The reverse happens in the self-healing tumours which have an inherited fault in the TGFBR1 gene. Patients with faulty TGFBR1 develop lots of small tumours – but at some point there is a ‘switch’ in behaviour and the tumours lacking TGFBR1 heal themselves. Scientists do not yet understand how this happens.
Dr David Goudie, Cancer Research UK scientist in the College of Medicine, Dentistry and Nursing at the University of Dundee, said: “The unusual behaviour of this tumour has baffled scientists for about 40 years so we’re excited to have discovered the genetic faults that cause the disease.
“The gene we’ve identified controls part of a cell signalling pathway which is faulty in many cancers. We hope that by shedding light on how one rare cancer manages to heal itself we’ll understand more about what goes wrong in other types of tumours.
“There’s also a lot of interest in drugs that target these signals. Understanding how tumours that lack TGFBR1 behave will help us to predict the clinical effects of these drugs.”
MSSE is very rare. Only a handful of new cases are diagnosed in the UK each year.
Dr Lesley Walker, director of cancer information, Cancer Research UK, said:
“This intriguing research provides an important insight into the various ways that cellular machinery can get messed up – which can then cause different types of cancer.
“This finding adds to thousands of discoveries being made by our world-class scientists every year. The pace of progress in cancer research is accelerating every year – enabling us to develop better ways to detect, monitor and treat the disease. This piece of research is another step – moving ever closer to our vision of beating cancer.”
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*Goudie, D’Alessandro et al. Nature Genetics. Multiple Self-Healing Squamous Epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.
Notes to editors
**The team collaborated with colleagues from the Institute of Medical Biology, Biomedical Research Council, A*STAR, Singapore, and the Department of Human Genetics, David Geffen School of Medicine at UCLA, and clinical colleagues from around the world.