Immune DNA signature of T-cell infiltration in breast tumor exomes.
Immune DNA signature of T-cell infiltration in breast tumor exomes.
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DOI：
10.1038/srep30064
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发表时间：
2016-07-25
影响因子：
4.6
通讯作者：
Harismendy O
中科院分区：
文献类型：
--
作者：
Levy E;Marty R;Gárate Calderón V;Woo B;Dow M;Armisen R;Carter H;Harismendy O
肿瘤浸润淋巴细胞（TIL）与多种肿瘤类型的良好预后相关。癌症基因组图谱（TCGA）代表了最大的癌症分子数据集，但缺乏有关免疫环境的详细信息。在这里，我们显示了映射到成熟T细胞受体β（TCRB）的互补决定区3（CDR 3）的外显子组读段可以用作免疫DNA（iDNA）签名。具体而言，我们提出了一种方法来识别乳腺肿瘤外显子组中的CDR 3读段，并使用深度TCRB测序对其进行验证。在1，078个TCGA乳腺癌外显子组中，CDR 3读段的分数与TIL分数、肿瘤纯度、适应性免疫基因表达特征和Her 2+患者的存活率改善相关。只有2/839的TCRB克隆型在患者之间共享，并且与特定的HLA等位基因或体细胞驱动突变无关。iDNA生物标志物丰富了通过TCGA收集的综合数据集，揭示了与其他分子特征和临床结果的关联。
Tumor infiltrating lymphocytes (TILs) have been associated with favorable prognosis in multiple tumor types. The Cancer Genome Atlas (TCGA) represents the largest collection of cancer molecular data, but lacks detailed information about the immune environment. Here, we show that exome reads mapping to the complementarity-determining-region 3 (CDR3) of mature T-cell receptor beta (TCRB) can be used as an immune DNA (iDNA) signature. Specifically, we propose a method to identify CDR3 reads in a breast tumor exome and validate it using deep TCRB sequencing. In 1,078 TCGA breast cancer exomes, the fraction of CDR3 reads was associated with TILs fraction, tumor purity, adaptive immunity gene expression signatures and improved survival in Her2+ patients. Only 2/839 TCRB clonotypes were shared between patients and none associated with a specific HLA allele or somatic driver mutations. The iDNA biomarker enriches the comprehensive dataset collected through TCGA, revealing associations with other molecular features and clinical outcomes.
在具有 DNA 修复缺陷的细胞中，外显子组范围内的体细胞微卫星变异发生了改变。
影响因子：
3.7
作者：
Vaksman Z;Fonville NC;Tae H;Garner HR
通讯作者：
Garner HR