Dr Andrew South, PhD, Associate Professor in the department of Dermatology and Cutaneous Biology at Jefferson (Philadelphia University + Thomas Jefferson University) 

Genetics of Aggressive Skin Cancers in Patients with ‘Butterfly’ Skin Identified

MedicalResearch.com Interview with:

Dr Andrew South, PhD, Associate Professor in the department of Dermatology and Cutaneous Biology at Jefferson (Philadelphia University + Thomas Jefferson University) 

Dr. South

Dr Andrew South, PhD,
Associate Professor in the department of Dermatology and Cutaneous Biology at Jefferson (Philadelphia University + Thomas Jefferson University) 

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by Butterfly Syndrome or recessive dystrophic epidermolysis bullosa?

Response: Epidermolysis Bullosa, or EB, is a group of genetic diseases caused by mutations in genes which play a role in maintaining skin integrity. An EB patients’ skin can be very fragile which has been likened to butterfly wings, which are also very fragile. Skin blisters are common in EB patients and in some cases large wounds can result from the slightest mechanical trauma, hence the term Butterfly Syndrome.

Skin cancer is a major complication of patients with the recessive dystrophic subtype of EB, known as recessive dystrophic epidermolysis bullosa or RDEB, and these cancers, called squamous cell carcinoma (SCC), are very aggressive. SCC is the leading cause of death in patients with RDEB. SCC also arise very early, affecting RDEB patients in their 20’s and 30’s. Our study used genetic analysis of cancers collected from patients to try and determine what causes the cancer at such an early age and what causes these cancers to be so fatal. Skin SCC arising in the general population as a result of sun exposure are generally benign and occur much later in life, regular skin SCC patients are predominantly over the age of 60, therefore something must be different about RDEB SCC. 

MedicalResearch.com: What are the main findings?

Response: We show that the genes which are mutated in RDEB SCC are the same as genes which are mutated in other types of SCC, such as skin or oral cavity SCC, and therefore do not explain the early onset or aggressive nature of RDEB SCC. However, we show that RDEB SCC have as many mutations as oral cavity SCC but are acquired in half the time, identifying that there is an accelerated mutation rate in RDEB. We show that this is not due to a DNA repair defect, rather it is due to the patient’s own cells responding to tissue damage by increasing the expression of a group of enzymes collectively called APOBEC. These enzymes are important in other types of cancer and here we identify tissue damage as a definitive mechanism for their cancer promoting activities. As well as these major findings we also identify greater similarity between RDEB SCC and subsets of oral SCC, rather than with skin SCC. This was determined by examining gene expression in data from all different types of SCC. Collectively these findings support RDEB as a model of aggressive SCC in the oral cavity. Furthermore RDEB SCC should be treated clinically as the same as oral cavity SCC, rather than skin SCC, and this is a direct clinical benefit for patients. Finally, we show that RDEB SCC are more homogenous, or clonal, than other cancers and this may be of benefit when considering targeted approaches to treatment as heterogeneity and polyclonality in cancer can be a major barrier to treatment. 

MedicalResearch.com: What should readers take away from your report?

Response: That APOBEC is a major mechanism driving mutation in cancers at sites of chronic tissue damage such as those in patients with RDEB.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We are exploring the mechanisms of APOBEC induction and APOBEC-driven tumor formation and trying to identify inhibitors of certain APOBEC enzymes which might have application for tumor prevention. The fact that we do not identify a particular pathway or mutation profile that explains the aggressive nature of RDEB SCC suggests that future research into understanding why these cancers, and potentially others, are so aggressive should focus on the tumor microenvironment.

No disclosures that are relevant to the publication.


Raymond J. Cho, Ludmil B. Alexandrov, Nicoline Y. den Breems, Velina S. Atanasova, Mehdi Farshchian, Elizabeth Purdom, Tran N. Nguyen, Cristian Coarfa, Kimal Rajapakshe, Marco Prisco, Joya Sahu, Patrick Tassone, Evan J. Greenawalt, Eric A. Collisson, Wei Wu, Hui Yao, Xiaoping Su, Christina Guttmann-Gruber, Josefina Piñón Hofbauer, Raabia Hashmi, Ignacia Fuentes, Stephen C. Benz, Justin Golovato, Erik A. Ehli, Christel M. Davis, Gareth E. Davies, Kyle R. Covington, Dedee F. Murrell, Julio C. Salas-Alanis, Francis Palisson, Anna L. Bruckner, William Robinson, Cristina Has, Leena Bruckner-Tuderman, Matthias Titeux, Marcel F. Jonkman, Elham Rashidghamat, Su M. Lwin, Jemima E. Mellerio, John A. McGrath, Johann W. Bauer, Alain Hovnanian, Kenneth Y. Tsai, Andrew P. South. APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa. Science Translational Medicine, 2018; 10 (455): eaas9668 DOI: 10.1126/scitranslmed.aas9668

[wysija_form id=”3″]

Sep 1, 2018 @ 5:05 pm


The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.