Analysis of multiple basal cell carcinomas (BCCs) arising in one individual highlights genetic tumor heterogeneity and identifies novel driver mutations

Abstract

Basal cell carcinoma (BCC) is the most common human cancer, especially in individuals with light skin phototypes (i.e., Fitzpatrick I‐II skin type). Many affected develop multiple BCCs during their lifetime. It is not uncommon to observe elderly patients with >5 BCCs. In this study, we explored whether for patients diagnosed with multiple BCCs, analyzing the genomic mutations in one tumor could be sufficient to derive meaningful molecular/genetic conclusions regarding the other BCC tumors. Following the Genome Analysis Toolkit (GATK) best practices we have completed the study of 6 BCCs that occurred in an 83‐year‐old Caucasian male due to sun exposure. We have analyzed exome sequencing data of each BCC tumor and matched normal skin samples. We identified that BCCs from the same patient shared some of the key driver mutations, but they also displayed significant intertumoral heterogeneity. This finding may in part explain the different clinical progression/evolution of BCCs observed in the same patient. This work also highlights the value of characterizing multiple BCCs in one individual to identify patient‐specific genetic events with a potential link to other malignancies and implications for personalized medicine.

National trends in incidence and geographic distribution of melanoma and keratinocyte carcinoma in the Russian Federation

“…KCs, also known as Non-Melanoma Skin Cancers (NMSC), are the most common cancers affecting fair-skinned individuals and include BCCs and cSCCs (4). Some of the risk factors for these cutaneous malignancies include a fair skin phototype, ultraviolet radiation (UVR) exposure, history of sunburn, genetic factors/mutations (e.g., mutations in the MC1R gene) and photoprotective behaviors (5)(6)(7)(8)(9).…”

The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review

“…NMSC is an umbrella term for all cutaneous malignancies that are not derived from melanocytes [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Keratinocyte carcinoma (KC) is the most prevalent subclass of NMSC [ 22 , 23 , 24 , 25 ]. KCs arise from subpopulations of interfollicular epidermal keratinocytes and hair follicle stem cells [ 26 , 27 , 28 , 29 ].…”

The Contributions of Cancer-Testis and Developmental Genes to the Pathogenesis of Keratinocyte Carcinomas

“…BCC arises from keratinocytes in the basal layer of the interfollicular epidermis, mechanosensory niches and from hair follicle infundibulum stem cells [ 29 ]. Mutations in the Sonic Hedgehog (Shh)-Patched 1 (PTCH1) signaling axis are integral to BCC tumorigenesis [ 30 ]. Seventy to ninety percent of sporadic BCCs exhibit PTCH1 loss-of-function mutations and 10–30% exhibit smoothened gain-of-function mutations [ 31 ].…”