Age Associated Mutation in Cutaneous Squamous Cell Carcinoma


Cutaneous squamous cell carcinoma was the most frequent type of skin cancer globally. The presence and frequency of poor prognostic indicators (TP53 or TERT promoter mutations) and therapeutic targets (ERBB4) were unknown about age. For a study, researchers sought to use cBioPortal to search the American Association for Cancer Research (AACR) Project GENIE database for cutaneous squamous carcinomas. Investigators gathered genetic changes and demographic data by age group (65 years, 66-80 years, >81 years) at the time of tumor sequencing. OncoKB was used to examine the function of genomic changes. The Chi-squared approach was used to compare descriptive variables reported as frequencies. The database contained 285 total CSCC samples among 1,025 non-melanoma skin cancer samples. By age category, 104 (36%) samples came from those aged 65 and under, 127 (45%) from those aged 66 to 80, and 54 (19%) from those aged more than 80. The prevalence of TP53 mutations rose with age, with 72% in those under 65, 88% between 66 and 80, and 93% in those over 80 (P<0.001). TP53 mutations were nearly all functional (96%; 228/237). ROS1 mutations were also more common as people got older, with 27% in those under 65, 37% in those 66-80, and 48% in those over 80 (P=0.03). All ROS1 mutations, on the other hand, were variations with unclear significance (VUS). TERT changes were also more common as people got older, with 32% in those under 65, 45% in those 66-80, and 46% in those over 80 (P=0.078). ERBB4 mutations also rose with age, with 28% in those under 65, 30% in those 66-80, and 33% in those over 80 (P=0.71); however, only 9/130 (6.9%) were known oncogenic mutations. In the AACR GENIE population, tumor suppressor genes (such as TP53, TERT, KMT2D, NOTCH1, NOTCH2, and FAT1) were often changed in CSCC, whereas actionable mutations and gain of function driving mutations (such as ERBB4) were uncommon.



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