Arthritis Drug May Increase Risk for Skin Cancer
Researchers from the University of Dundee in the United Kingdom have identified a correlation between a mutational signature in cutaneous squamous cell carcinoma and length of treatment with azathioprine.
Azathioprine, an immunosuppressive therapeutic, is commonly used for the treatment of arthritis, inflammatory bowel disease, and vasculitis. It has also been known to increase photosensitivity to UVA light, which may contribute to skin cancer.
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To better understand this connection, the researchers conducted whole exome sequencing of 40 primary cutaneous squamous cell carcinoma tumors from 37 patients who were either immunosuppressed or immunocompetent. A majority of immunosuppressed patients had received azathioprine in combination with another immunosuppressant agent.
In addition, researchers performed a mutational signature analysis of 15 cutaneous squamous cell carcinoma-related cell lines.
Signature 32 was found in 27 samples from both well-differentiated or poor/moderately differentiated tumors but was most prevalent among immunosuppressed patients. Three tumors with signature 32 were found in patients who had received azathioprine alone.
Tumors of immunosuppressed patients who did not receive azathioprine did not have evidence of mutational signature 32.
Researchers observed a strong association between azathioprine exposure and signature 32, and no exposure to other immunosuppressant therapeutics.
No other significant associations were observed between mutational signatures and exposure to any immunosuppressant drug.
A strong correlation was also observed between the estimated length of azathioprine treatment and amount of signature 32.
“In summary, this study describes the complex molecular landscape of [cutaneous squamous cell carcinoma] and identifies new potential driver genes, pathways and processes associated with both the development of well-differentiated and potentially poorer prognosis moderately/poorly differentiated tumors in both immunosuppressed and immunocompetent patients,” the researchers concluded.
“Importantly we identify a novel mutational signature associated with chronic azathioprine exposure and describe the molecular landscape of 15 [cutaneous squamous cell carcinoma] cell lines derived from both primary and metastatic lesions, which reflect the complexity of tumors and provides a unique resource for determining the biological significance of the molecular events responsible for [cutaneous squamous cell carcinoma] maintenance and progression.”
—Melinda Stevens
Reference:
Inman GJ, Wang J, Nagano A, et al. The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature [Published online September 10, 2018]. Nat Commun. https://doi.org/10.1038/s41467-018-06027-1.