Background: Mycosis fungoides (MF) is a rare cutaneous T-cell lymphoma (CTCL) that presents clinically on the skin as patches, plaques, or tumors. MF often mimics benign inflammatory conditions which leads to difficult and delayed diagnosis, worsening prognosis despite available treatment options. This study seeks to improve diagnosis and identify potential therapeutic targets by better characterizing MF’s genetic landscape using the AACR Project GENIE dataset. Methods: Retrospective analysis of MF cases was conducted using the AACR Project GENIE database accessed from cBioPortal (v17.0-public) on 5 June 2025. Data analysis included identifying recurrent somatic mutations, assessing patterns of mutation co-occurrence and mutual exclusivity using non-parametric tests with Benjamini–Hochberg False Discovery Rate (FDR) correction, and examining enrichment of specific mutations based on sex and race, with significance ofp< 0.05. Results: Recurrent alterations includedFAT1(28.2%),KMT2D(19.2%),TP53(13.5%),JAK3(11.5%), andSETBP1(11.5%), highlighting the role of Wnt signaling, epigenetic dysregulation, the p53 pathway, and JAK/STAT signaling in MF pathogenesis. Mutations with significant co-occurrence and enrichment in White, Black, and Asian populations were identified. Conclusions: The findings of this study provide a comprehensive understanding of MF’s molecular profile. The discovery of commonly mutated pathways (Wnt, p53, JAK/STAT, and epigenetic regulators) suggests potential targets for the development of future therapies. Furthermore, the enrichment of certain mutations based on race and patterns of alteration co-occurrence offer possibilities for patient-tailored treatment approaches.
背景：蕈样肉芽肿是一种罕见的皮肤T细胞淋巴瘤，临床表现为皮肤斑片、斑块或肿瘤。该病常与良性炎症性疾病表现相似，导致诊断困难且延迟，尽管已有多种治疗方案，但预后仍可能恶化。本研究旨在利用AACR项目GENIE数据集，通过深入解析蕈样肉芽肿的基因图谱，以改善诊断并识别潜在治疗靶点。方法：通过cBioPortal平台（v17.0-public）于2025年6月5日获取AACR项目GENIE数据库，对蕈样肉芽肿病例进行回顾性分析。数据分析包括识别高频体细胞突变、采用经Benjamini-Hochberg错误发现率校正的非参数检验评估突变共现与互斥模式，并基于性别和种族分析特定突变的富集情况，显著性阈值设定为p<0.05。结果：高频基因变异包括FAT1（28.2%）、KMT2D（19.2%）、TP53（13.5%）、JAK3（11.5%）和SETBP1（11.5%），凸显了Wnt信号通路、表观遗传失调、p53通路及JAK/STAT信号通路在蕈样肉芽肿发病机制中的作用。研究同时识别了在白人、黑人和亚洲人群中显著共现及富集的突变类型。结论：本研究系统揭示了蕈样肉芽肿的分子特征谱。常见突变通路（Wnt、p53、JAK/STAT及表观遗传调控因子）的发现为未来疗法开发提供了潜在靶点。此外，基于种族的特定突变富集现象及变异共现模式，为制定个体化治疗方案提供了新思路。
Integrative Mutational Landscape of Mycosis Fungoides Using a National Genomics Repository
肿瘤(癌症)患者之家