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，多个研究团队针对皮肤T细胞淋巴瘤（cutaneous T-cell lymphoma, CTCL）开展了测序研究，以期识别驱动疾病发生的突变。整合多队列数据的基因组数据集，有助于开展更为全面的疾病通路研究及CTCL的基因组分型，但目前尚无此类公开数据集可用。本研究整合并分析了一套此类数据集，该数据集包含139例CTCL患者的配对基因组突变与拷贝数变异数据。基于该数据集，我们针对高频突变通路中的突变互斥性、以及突变负荷与其他参数关联的生存曲线展开了研究。我们发现，核因子κB（NFκB）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基因突变同样呈互斥状态。我们未观察到携带与不携带p53或核因子κB通路基因突变的塞扎里综合征（Sezary Syndrome, SS）患者总生存期存在显著差异，但基因组突变负荷最高与最低的塞扎里综合征患者，其总生存期则存在差异。上述研究结果提示，可依据潜在致病通路对CTCL进行分型，且有望通过针对患者特异性突变的选择性靶向治疗，实现CTCL的个体化诊疗。