Is the presence of Merkel cell polyomavirus and human papillomavirus DNA in keratinocyte cancers and precancers associated with HIV status? A case-control study.

The epidemiology and potential pathogenic roles of human papillomavirus (HPV) and Merkel cell polyomavirus (MCV) in keratinocyte cancers (KCs) arising in people living with HIV (PLWH) compared with HIV-negative individuals are poorly understood. These issues were investigated by a case-control study in which the presence of MCV and HPV DNA was identified by polymerase chain reaction in microdissected formalin-fixed paraffin-embedded tissue from PLWH and HIV-negative individuals. The samples comprised 190 cutaneous and genital KCs/precancers (actinic keratoses, n = 43; cutaneous squamous cell carcinoma (cSCC) in situ, n = 24; basal cell carcinoma, n = 78; cSCC, n = 34; penile carcinoma in situ, n = 9; penile SCC, n = 2 from 104 individuals (PLWH, n = 51; HIV-negative, n = 53).

The Genomic Landscape of Actinic Keratosis.

Actinic keratoses (AKs) are lesions of epidermal keratinocyte dysplasia and are precursors for invasive cutaneous squamous cell carcinoma (cSCC). Identifying the specific genomic alterations driving the progression from normal skin to skin with AK to skin with invasive cSCC is challenging because of the massive UVR-induced mutational burden characteristic at all stages of this progression. In this study, we report the largest AK whole-exome sequencing study to date and perform a mutational signature and candidate driver gene analysis on these lesions.

A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing.

Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to rise with increasing morbidity and mortality, with limited treatment options for advanced disease. Future improvements in targeted therapy will rely on advances in genomic/transcriptomic understanding and the use of model systems for basic research. We describe here the panel of 16 primary and metastatic cSCC cell lines developed and characterised over the past three decades in our laboratory in order to provide such a resource for future preclinical research and drug screening.

Epigenetic Regulation of iASPP-p63 Feedback Loop in Cutaneous Squamous Cell Carcinoma.

Keratinocyte skin cancer, comprising cutaneous squamous (cSCC) and basal cell carcinoma, is the most common malignancy in the United Kingdom. P53 is frequently mutated in cSCC. iASPP is a key inhibitor of p53 and NF-κB signaling pathways and has been documented as highly expressed in several types of human cancer.