荔枝视频

Researchers have used specialized genomic technology at the 荔枝视频 to enhance our understanding of Marjolin鈥檚 ulcer (MU), a rare, highly aggressive skin cancer that may arise from established scars like those caused by severe burns.  

鈥淭he longer you live with a chronic wound like a burn, the higher your risk of developing Marjolin鈥檚 ulcer," says Dr. Jeff Biernaskie, PhD, principal investigator and 荔枝视频 Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing. 鈥淭he more we know about underlying cellular interactions within the wound and how these cells are driven to become cancerous, the more likely we will be able to find a treatment which would be life-saving.鈥� 

The research team completed a cell-by-cell analysis to better understand how MU tumours grow. Using both single cell ribonucleic acid (RNA) sequencing and spatial transcriptomics available at U荔枝视频鈥檚  (CHGI), they did precise mapping of gene expression and cellular interactions within a tumor. With that enhanced view the researchers could trace how a small subtype of skin cells (keratinocytes) switch their function to start behaving like a type of support cell (fibroblast) that creates the conditions that encourage tumor cells to grow.

鈥淭he cancerous keratinocytes appear to undergo a 鈥榗areer change,鈥� shifting from their original role as outer skin cells to adopting new characteristics resembling dermal fibroblasts, which are the support cells found deeper in the skin,鈥� says Sarthak Sinha, MD/PhD candidate and lead author. 鈥淭his transformation also enables them to start producing a type of extracellular matrix that is similar to what is found in developing skin. This new matrix essentially acts like fertile soil, creating the perfect environment for the cancer cells 鈥� the seeds 鈥� to take root, grow aggressively and spread to nearby structures. 

"It鈥檚 this interaction between the 鈥榮eed鈥� and the 鈥榮oil鈥� that may drive the tumour鈥檚 invasive behavior. We believe this process plays a role not only in Marjolin鈥檚 ulcer but also in other skin cancers, contributing to poor patient outcomes."

Image above, top left: Clinical photograph depicts Marjolin鈥檚 ulcer (MU) emerging from burn scar. Top right: Histological section showing the transition from burn scar tissue to MU. Bottom: Spatial genomic imaging reveals the distribution of various cell types at the microscopic level. Each color corresponds to a different cell population, offering insights into the cellular milieu of MU and its progression from the adjacent scar tissue.

Dr. Vincent Gabriel, MD, medical director of the , says insight into how these tumours start and thrive may also help to identify potential treatments to try to prevent the tumour from metastasizing. 

鈥淭his study identifies opportunities for targeting the process that leads to Marjolin鈥檚 cancer itself. A combination of surgical excision and medical intervention may limit the effect of these aggressive tumours,鈥� says Gabriel, who is also an associate professor at the and co-author of the study. 鈥淪uccessful treatments could offer greater peace of mind to burn survivors, especially those who may be highly prone to these cancers, providing significant relief after their challenging medical journeys.鈥�

Gabriel says MU can also be difficult to diagnose because a biopsy of the wound can miss the cancerous cells that are not uniform within the wound. The researchers say it is gratifying to share what they鈥檝e learned with the hope someone will take it and learn more to help those diagnosed with aggressive skin cancers. The  in the Journal of Investigative Dermatology.  

The research was supported by the Department of Surgery鈥檚 Surgical Research Development Fund and 荔枝视频 Firefighters Burn Treatment Society.

Co-authors of the study include Dr. Nicole Rosin, PhD; Rohit Arora, PhD candidate; Eren Kutluberk, PhD candidate; Dr. Myriam Verly, MD; Caleb Small, BHSc student; Aydin Herik, MD candidate; Lindsay Burnett, nurse practitioner; Leslie Cao, biomedical engineering student; Varsha Manoharan, PhD Candidate; Keerthana Chockalingam, BHSc student; Dr. Marieta van der Vyver, MD; Dragana Ponjevic, researcher; Dr. Holly Sparks, DVM, PhD; Dr. Sorana Morrissy, PhD; Dr. Ana Nikolic, MD, PhD; Dr. Robertson Harrop, MD; Dr. Thomas Brenn, MD, PhD; and Dr. Claire Temple-Oberle, MD.