Arron Lab

High Risk Skin Cancer Program

University of California, San Francisco

The Arron laboratory investigates the genomics and metagenomics of cutaneous squamous cell carcinoma in organ transplant recipients.

Squamous cell carcinoma (SCC) is the second most common type of skin cancer, with an estimated incidence of over 200,000 cases per year in the United States and a 65-fold increased risk in immunosuppressed organ transplant recipients over the general population.

This magnitude of risk implies a viral etiology, but no viral agent has been definitively identified. Another hypothesis is that failure of immune surveillance predisposes transplant recipients to SCC. These hypotheses are not mutually exclusive;  immunosuppression can predispose to viral infection and to skin cancer.

A primary research question for our group is whether there is a viral etiologic agent in SCC in immunosuppressed patients and in the general population. Human papillomavirus (HPV) has been implicated in SCC formation, but the mechanism is unclear.  HPV DNA in the skin correlates with age and immunosuppression, but viral transcription is not detected in cutaneous SCC. This implies that a viral agent must use an alternate mechanism of oncogenesis.

The cutaneous oncoviruses: HHV-8, HPV, and MCV.  All three express proteins that interfere with cell cycle regulation.

Risk factors for SCC following organ transplantation include older age at transplant, fair skin, and male sex.  Certain medications appear to increase this risk as well.  We seek to address the interaction between genetic risk factors and exogenous agents in our clinical cohort, OTR2.  This cohort is currently being followed in the High Risk Skin Cancer Clinic at the UCSF Dermatologic Surgery and Laser Center.  This clinic is devoted to the investigation and care of patients at risk for skin cancer due to solid organ transplant and other iatrogenic immunosuppression, HIV infection, and genetic conditions predisposing to cutaneous malignancy.

Low levels of HPV in cutaneous SCC.  Higher DNA viral loads are associated with age and immunosuppression.

TP53 mutations precede loss of heterozygosity on chromosome 17 of SCC.

Tumorigenesis may occur in the absence of viral infection.  Oncogenesis appears to be triggered by TP53 mutation, followed by loss of heterozygosity and accumulation of various passenger mutations.  Biallelic mutations also occur in Notch.