Data from: An integrated data resource for genomic analysis of cutaneous T-cell lymphoma

Recently, several groups have conducted sequencing studies of cutaneous T-cell lymphoma (CTCL) in order to identify disease driving mutations. An integrated genomic dataset that combines multiple cohorts may facilitate more comprehensive studies of disease pathways and genomic classification of CTCL, but currently no such resource is available. In this study we compiled and analyzed one such dataset that included matched genomic mutations and copy number alterations of 139 CTCL cases. Using this dataset, we studied mutual exclusivity of mutations in the most frequently mutated pathways and survival curves depending on mutation load and other parameters. We found that mutations in the NFkB pathway genes PLCG1, CARD11 and TNFRSF1B were mutually exclusive. Mutations in the NFkB pathway genes and those in p53 were also mutually exclusive. No significant difference in overall survival was seen between SS cases with or without mutations in p53 or the NFkB pathway genes. There was a difference in overall survival between SS cases with the most and the fewest mutations in the genome. These results suggest the possibility of classifying CTCL by underlying pathogenic pathways and the potential for selective targeting of CTCL by patient-specific mutations in order to personalize CTCL therapies.

近年来，多个研究团队开展了皮肤T细胞淋巴瘤（cutaneous T-cell lymphoma, CTCL）的测序研究，以期识别疾病驱动突变。整合多队列数据的基因组数据集或可助力开展疾病通路及皮肤T细胞淋巴瘤基因组分型的全面研究，但目前尚无此类可用资源。本研究整合并分析了一套此类数据集，该数据集涵盖139例皮肤T细胞淋巴瘤患者的匹配基因组突变与拷贝数变异数据。依托该数据集，我们分析了高频突变通路中突变的互斥性，并探究了突变负荷及其他参数与生存曲线的关联。我们发现，核因子κB（NF-κB）通路基因PLCG1、CARD11与TNFRSF1B的突变呈互斥状态；核因子κB通路基因的突变与p53突变同样呈互斥状态。携带与不携带p53或核因子κB通路基因突变的塞扎里综合征（Sezary syndrome, SS）患者，总生存期无显著差异；但基因组突变最多与最少的塞扎里综合征患者，总生存期存在显著差异。上述结果表明，可依据潜在致病通路对皮肤T细胞淋巴瘤进行分型，且可通过患者特异性突变实现皮肤T细胞淋巴瘤的选择性靶向治疗，为个体化治疗提供可能。

搜集汇总

背景与挑战

背景概述

该数据集是一个用于皮肤T细胞淋巴瘤（CTCL）基因组分析的整合资源，包含139个病例的基因组突变和拷贝数变异数据，旨在支持疾病通路研究和基因组分类。数据集通过分析NFkB通路基因与p53基因突变的互斥性，以及突变负荷与生存率的关系，为个性化治疗提供潜在依据。