Advanced genomics reveals new insights into Marjolin ulcers, aiding skin cancer treatment.

Researchers at the University of Calgary are using the university's advanced genomics technologies to improve understanding of Marjolin ulcer (MU), a skin cancer that typically affects individuals who suffer from chronic wounds, particularly those caused by severe burns.

As the duration of chronic wounds increases, an individual's risk of developing a Marjolin ulcer also rises. By gaining insights into the cellular interactions within wounds and how they become cancerous, scientists hope to discover life-saving treatments. "The more we understand about how these cells interact and how they turn into cancer cells, the more likely we are to find effective treatments," said researcher Dr. Jeff Biernaskie, who is also the Calgary Firefighters Burn Care Association Chair in Skin Regeneration and Wound Healing.

The research team used single-cell RNA sequencing and spatial transcriptomics to precisely analyze gene expression and cellular interactions within MU tumors. These technologies, provided by the University of Calgary's Centre for Health Genomics and Informatics (CHGI), enabled the researchers to track how a subtype of skin cells (keratinocytes) switched their function and began behaving like supporting cells (fibroblasts), thus creating conditions for tumor cell growth.

"Cancerous keratinocytes appear to undergo a 'career switch,' shifting from their original role as cells of the outer layer of skin to a new role with characteristics of dermal fibroblasts, supportive cells in the deeper layers of the skin," explains author and PhD candidate Sarthak Sinha. "This switch also enables them to produce an extracellular matrix similar to that in developing skin, providing a fertile growth environment for cancer cells, promoting the aggressive behavior of tumors."

Dr. Vincent Gabriel, medical director of the Calgary Firefighters Burn Centre, noted that gaining insight into how tumors develop and grow may help identify potential treatments to prevent them from metastasizing. "This study reveals potential therapeutic opportunities that target the process by which Marjolin cancers develop. Combining surgical resection with medical intervention may help limit the impact of these aggressive tumors." Dr. Gabriel added that successful treatment could bring comfort to burn survivors, especially after a difficult medical journey.

Dr. Gabriel also mentioned that because MU is difficult to diagnose, wound biopsies may miss unevenly distributed cancer cells. The researchers look forward to sharing their findings to help those diagnosed with aggressive skin cancer. The results of this study have been published in the Journal of Investigative Dermatology.

Source:

University of Calgary

Journal reference:

Sinha, S., et al. (2024). Spatial and single-cell transcriptomics reveals tumoral fetal reprogramming of fibroblasts associated with malignant degeneration of burn scars. Journal of Dermatological Research.