Chromophobe renal cell carcinoma (chRCC) is a distinct subtype of non–clear cell renal cell carcinoma (ncRCC), arising from intercalated cells of the distal nephron collecting ducts. No standard treatments are specifically approved for chRCC, which is further hindered by lack of a universally accepted grading system. This study sought to find molecular drivers that may aid in the diagnosis or development of treatments for chRCC. A retrospective analysis of chRCC was conducted using data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) repository, accessed through cBioPortal (version 17.0-public) on 21 July 2025. The study examined recurrent somatic mutations and assessed co-occurrence with Benjamini–Hochberg False Discovery Rate (FDR) correction. Additional analyses evaluated mutation by sex and race, with significance set at p < 0.05. The cohort included 180 tumor samples from 170 chRCC patients. Most patients were adults (n = 167, 98.2%) and White (n = 115, 67.6%). Recurrent alterations occurred in genes part of the p53, PI3K/mTOR, Hippo, and NOTCH signaling pathway. Exploratory demographic analyses identified isolated single-patient mutations in select genes across sex and race; however, these rare events are not interpretable as population-level differences. This study provides a comprehensive genomic profile of chRCC across multiple demographic categories.

Background and Objectives: Cervical adenocarcinoma (CAC) is a histologically distinct subtype of cervical cancer with a rising incidence in many regions. While the roles of key driver mutations are known, a comprehensive understanding of its genomic landscape, particularly variations across different populations and tumor stages, remains incomplete. This study aims to characterize the somatic genomic landscape of CAC by identifying recurrent mutations, copy number alterations (CNAs), and patterns of co-occurrence, with a focus on variations across racial groups and between primary and metastatic tumors. Materials and Methods: We conducted a comprehensive genomic analysis of 102 tumor samples from 99 patients diagnosed with cervical adenocarcinoma using data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database. Results: The most frequently mutated genes were PIK3CA (25.5%), TP53 (21.6%), ARID1A (20.6%), and KRAS (16.7%). Significant amplification of ERBB2 was also observed (n = 3; 4.83%). Our analysis revealed notable genomic disparities across racial groups, with TP53 mutations being significantly more frequent in White patients compared to Asian and Black patients (p = 0.0236). Furthermore, we identified significant co-occurrence between mutations in KRAS and MSH2 (p = 0.011) as well as ATM and STK11 (p = 0.037). In comparing tumor types, mutations in BCL6 were found to be significantly enriched in metastatic samples. Conclusions: This study validates the primary drivers of cervical adenocarcinoma and reveals novel findings, including notable racial disparities in TP53 mutation frequency and unique patterns of co-occurring mutations. These findings highlight the genomic heterogeneity of the disease and suggest that ancestry and tumor evolution may influence its molecular pathogenesis, offering potential avenues for the development of targeted therapies and personalized biomarkers.