Somatic genomic landscape of prostate adenocarcinoma at a comprehensive cancer center in New Mexico: A retrospective study (2015-2022).

Abstract

200 Background: Prostate cancer is the second leading cause of cancer-related deaths in men. In New Mexico, it is the leading cause of cancer death among specific populations, particularly American Indians and African Americans. This study investigates the frequency and diversity of somatic mutations in patients with prostate adenocarcinoma treated at the University of New Mexico Comprehensive Cancer Center (UNMCCC). Methods: We conducted a retrospective analysis of patients with prostate adenocarcinoma treated at UNMCCC from 2015 to 2022 who underwent screening for somatic mutations via next-generation sequencing (NGS). We evaluated these mutations and collected data on tissue type tested, race, ethnicity, and age. Descriptive analysis summarized frequencies of somatic mutations overall and across ethnic groups. Due to small sample sizes, randomization tests were performed to evaluate whether mutation rates within ethnic groups differed significantly from those expected based on the ethnic composition of the entire sample. Results: The study examined 61 patients (median age 63 years) including: 31 White (51%), 16 Hispanic (26%), 9 American Indian (15%), 4 African American (7%), and 1 Asian (2%). Of the patients tested, 52 underwent tissue-based NGS, 7 had liquid-based NGS, and 2 had both tests performed. The most prevalent genetic alterations were TMPRSS2-ERG fusion (48%), TP53 mutations (41%), PTEN loss/rearrangement (36%), and AR mutations (30%). Comparisons of mutation frequencies across ethnic groups revealed variations in mutation prevalence (Table 1) For most mutations, observed ethnic group frequencies did not differ significantly from expected frequencies based on the total sample (p>0.05), although statistical power was low to detect all but large differences. The exception was BRCA2, where ethnic group frequencies differed significantly from those in the total sample (p=0.025), with no Hispanic patients and equal numbers of White and Native American patients having the mutation. Conclusions: This study reveals complex prostate cancer genetic patterns across diverse New Mexican ethnicities. These findings have potential implications for targeted therapies and emphasize the need for larger, more diverse cohorts in research. Proportion of race and ethnic groups with each mutation. Mutation Number Positive Proportions Within Racial/Ethnic Groups Hispanic Native American Black White Asian TMPRSS2:ERG fusion 29 24.1% 17.2% 0.0% 55.2% 3.4% TP53 25 24.0% 8.0% 8.0% 60.0% 0.0% PTEN loss/frameshift 22 27.3% 13.6% 4.5% 54.5% 0.0% AR Mutations 18 27.8% 5.6% 5.6% 61.1% 0.0% MYC amplification 11 45.5% 9.1% 0.0% 45.5% 0.0% PIK3CA 7 28.6% 28.6% 0.0% 42.9% 0.0% RAD51 R/RAD21 AMP 7 57.1% 14.3% 0.0% 28.6% 0.0% BRCA2 6 0.0% 33.3% 16.7% 33.3% 16.7% BRCA1 3 66.7% 0.0% 0.0% 33.3% 0.0% ATM 3 0.0% 33.3% 0.0% 66.7% 0.0% All Screened 61 26.2% 14.8% 6.6% 50.8% 1.6%