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Scientists discover cause of rare skin cancer that heals itself

Institute of Medical Biology (IMB) scientists under the Agency of Science, Technology and Research (A*STAR) in Singapore are part of an international team of researchers [1]who became the first in the world to discover the gene behind a rare skin cancer which grows rapidly for a few weeks before healing spontaneously, according to research published in Nature Genetics [2] today.

The peculiar behaviour of this rare self-healing cancer, called multiple self-healing squamous epithelioma (MSSE), was discovered to be caused by a failure in the gene called TGFBR1, which is a key component of a signalling pathway that can also be impaired in other cancers. This pathway is widely regarded in the field as a potential target for therapeutic intervention in cancer treatment.

Dr David Goudie, a Clinical Genetics consultant at Dundee University and a long term specialist in MSSE, said: “The unusual behaviour of this tumour has baffled scientists for over 40 years, so we’re excited to have discovered the genetic faults that cause the disease. Understanding how tumours that lack TGFBR1 behave will surely help us to predict the clinical effects of drugs that target these cancer-promoting or cancer-inhibiting signals.”

Said Professor Birgit Lane, the team leader and Executive Director of IMB, “We started working on this in Dundee nearly 10 years ago, but it was not until we were able to apply new approaches to the problem, through the links we have developed in Singapore, that we were together able to identify the cause of the disease.”

However, Professor Birgit Lane cautioned, “The TGFBR1 gene is also part of a very important cell signalling system that is essential for many normal processes. Though it has been implicated in many other cancers before now, one cannot just go around blocking its function indiscriminately. We hope that this new found knowledge on an unusual self-healing tumour will open a door to new ways of tweaking the cell machinery more selectively in cancer therapy.”

About TGFBR1 and MSSE

The TGFBR1 (Transforming Growth Factor (Beta), Receptor 1) gene makes a receptor protein through which healthy cells receive messages from their neighbours, instructing them to carry out processes essential to normal growth and development. Normally, TGFBR1 messages help block the growth of early tumours of various types. But cancer cells can interpret these messages very differently. For cancers that have managed to start growing, TGFBR1 actually promotes their growth and spread instead.

Interestingly, the reverse happens in the self-healing tumours that have an inherited fault in the TGFBR1 gene. MSSE patients with faulty TGFBR1 develop lots of small tumours — but at some point there is a switch in behaviour and the tumours lacking TGFBR1 start to shrink and heal by themselves. Scientists do not yet fully understand how this happens but the result of this study has raised new approaches to studying this important signalling system and its relation to cancer.

MSSE is an extremely rare disease, with only a handful of new cases diagnosed each year. International translational collaborations between doctors and scientists, like the one underlying this study, are critical to allow for scientific breakthroughs to be made that could lead to possible cancer therapy.

Notes to editors:

1. The collaborative team include A*STAR’s BMRC-funded Institute of Medical Biology (Singapore); Cancer Research UK-funded labs at the University of Dundee (UK); Department of Human Genetics, David Geffen School of Medicine at UCLA (USA) and clinical colleagues from around the world.

2. Goudie, D’Alessandro et al. Nature Genetics. Multiple Self-Healing Squamous Epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.

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About the Institute of Medical Biology (IMB)

IMB is one of the Biomedical Sciences Institutes of the Agency for Science, Technology and Research (A*STAR). It was formed in 2007, the 7th and youngest of the BMRC Research Institutes, with a mission to study mechanisms of human disease in order to discover new and effective therapeutic strategies for improved quality of life.

IMB hosts 20 research teams of international excellence in stem cells, genetic diseases, cancer and skin and epithelial biology, and works closely with clinical collaborators to target the challenging interface between basic science and clinical medicine. Its growing portfolio of strategic research topics is targeted at translational research on the mechanisms of human diseases, with a cell-to-tissue emphasis that can help identify new therapeutic strategies for disease amelioration, cure and eradication.

For more information about IMB, please visit www.imb.a-star.edu.sg.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and nine consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.

A*STAR supports Singapore’s key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, hospitals, research centres, and with other local and international partners.

For more information about A*STAR, please visit www.a-star.edu.sg.




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