Genetics and stem cells

Gene behind rare skin cancer found

“Scientists are a step closer to beating cancer after discovering how a rare type of the disease can heal itself,” reported the Daily Express . It said that this finding “could pave the way for new drugs to treat a range of tumours, including breast and bowel cancer”.

This story is based on research which identified the mutated gene that is responsible for a very rare skin cancer condition called multiple self-healing squamous epithelioma (MSSE). People with this condition have multiple skin tumours that grow rapidly for a few weeks before spontaneously healing, leaving only a scar. Now that researchers have identified the gene responsible, called TGFBR1, this will help them go on to investigate how the tumours heal.

Study of this rare condition may help scientists to better understand how tumours can form, and how they resolve themselves. However, there is much more research to be done. Whether this will lead directly to new treatments for other kinds of more common tumours remains to be seen.

Where did the story come from?

The study was carried out by researchers from the University of Dundee College of Medicine and other international research institutions. Cancer Research UK and the Biomedical Research Council (A*STAR) of Singapore funded the research. The study was published in the peer-reviewed journal: Nature Genetics .

The Daily Telegraph and the Daily Express covered this story.

What kind of research was this?

The aim of this genetics study was to identify the gene that causes a rare skin cancer condition called multiple self-healing squamous epithelioma (MSSE), or Ferguson-Smith disease. In this disease, multiple skin tumours form and grow rapidly for a few weeks but then spontaneously heal, leaving just scars. Previous studies have shown that this disease runs in families, and is caused by a mutation in a single gene located on the long arm of chromosome 9. However, the mutated gene had not yet been identified.

The methods used in this study are typical for this type of research. It is important to point out that most cancers are not caused by a mutation in a single gene but by a complex interplay of genetic and environmental factors. However, identifying the genes that cause these rarer cancers may potentially help researchers to understand more about the cancers with more complex causes.

What did the research involve?

The researchers used DNA from 143 individuals from 22 families affected by multiple self-healing squamous epithelioma (MSSE). At least half of these families were of Scottish ancestry.

To narrow down the genes that may be responsible for the cancer, the researchers used high-throughput techniques to ‘capture’ and sequence the 152 genes located in the region of DNA on chromosome 9 where the mutation was known to lie. They did this using DNA from 10 individuals: four affected pairs of parents and children from four unrelated families, and one parent-child pair from an unaffected control family.

They then looked for mutations in the DNA which occurred in the affected parents and children (but not in the controls) and which would be expected to affect the protein that was encoded by the gene. The mutation causing the disease is dominant, which means that a person only needs to carry one mutated copy of the gene to be affected. Therefore, the researchers also knew they were looking for a mutation that affected only one of the two copies of the gene carried by each person.

The researchers found a mutation in a gene that fulfilled these criteria. They sequenced this gene in all the 22 available families with MSSE to see if other individuals with the disease carried mutations in the same gene. They also sequenced the gene in 80 unrelated healthy Scottish individuals to make sure that mutations in this gene did not occur in healthy people.

The researchers then tested thin slices of MSSE tumours and normal skin to see whether the protein encoded by this gene was present.

What were the basic results?

Using high-throughput sequencing of the candidate region of chromosome 9, the researchers identified three different mutations in the transforming growth factor beta receptor 1 (TGFBR1) gene in individuals from three unrelated families affected by MSSE.

When they sequenced this gene in 22 families with MSSE, they found mutations in the TGFBR1 gene in 18 of the families. They sequenced 67 people with MSSE from these 18 families, and found that they all carried mutations in the TGFBR1 gene. They detected no TGFBR1 mutations in 80 unrelated healthy individuals from the Scottish population. The TGFBR1 protein was found in both normal skin and MSSE skin tumours.

The mutations identified would cause various changes to the TGFBR1 protein encoded by the gene, for example, changing one or more of the protein’s amino acids, or causing the protein to be shorter than normal. The TGFBR1 protein encoded by this gene sits in the membrane of the cells and binds to the signalling molecule TGF-β. Previous studies have found that TGF-β plays a role in cell growth and division, and that its effects on tumours can vary depending on their stage. TGF-β signalling normally restricts cell growth. It can also protect against early-stage cancer formation in mice, but it can increase the aggressiveness of later-stage tumours.

How did the researchers interpret the results?

The researchers conclude that their results “show another link between TGFBR1 and cancer and provide compelling evidence that mutations in TGFBR1 cause the self-healing skin tumors of MSSE”. They say that in light of this discovery, they can now better study why these tumours spontaneously heal themselves.


This study has identified the genetic mutation that causes the rare and unusual skin cancer condition, multiple self-healing squamous epithelioma or Ferguson-Smith disease. This condition is rare and unusual in that the skin tumours spontaneously get better, leaving just scarring.

Most cancers are not caused by a mutation in a single gene. They are the result of a complex interplay of genetic and environmental factors. However, better understanding of rare tumour-causing conditions caused by a single gene may help to understand the biology of other tumours better and, in this case, how they might heal themselves. A lot more research will be needed before researchers can fully understand the processes underlying this condition, and to determine their similarity to the processes leading to the formation of other skin cancers or other kinds of tumour.

At this stage, it is too early to say whether these findings will lead directly to new treatments for skin cancers or other kinds of tumours.

NHS Attribution