The Genetics of Early-Stage Melanoma in a Veteran Population

Abstract

To improve understanding of the genetic signature of early-stage melanomas in Veterans, hotspot mutation profiling using next-generation sequencing (NGS) was performed on melanoma tissue samples from patients at the Iowa City Veterans Affairs Medical Center (VAMC). Genetic analysis identified BRAF (36.3%), TP53 (25.9%), NRAS (19.3%), CDKN2A (11.1%), KIT (8.1%), and BAP1 (7.4%) mutations with the highest prevalence. Although common variants in BRAF were detected at lower rates than what is reported for the general population, 55.6% of cases showed activating mutations in the RAS/RAF pathways. Variants in TP53 and KIT were detected at higher rates than in the general population. Veterans with prior history of melanoma were at significantly higher odds of having TP53 mutation (OR = 2.67, p = 0.04). This suggests that TP53 may be a marker for recurrent melanoma and possibly alternative exposures in the military population. This study provides new information regarding the genetics of melanoma in a Veteran population and early-stage melanomas, highlighting risk factors unique to this population and contributing to the conversation about preventing melanoma deaths in US Military personnel.

Keywords: BRAF; TP53; genetic predisposition; melanoma; military personnel; proto-oncogene; risk factors; veterans.

Figure 1

Overlap of BRAF, TP53, and NRAS Mutations. Number of Veterans with melanoma harboring BRAF, TP53, and NRAS mutations out of our cohort of 135 Veterans are shown. A subset of melanomas has both BRAF and TP53 mutations and another subset has both NRAS and TP53 mutations. However, BRAF and NRAS mutations are mutually exclusive.