High-Throughput Genomic Profiling of Adult Solid Tumors Reveals Novel Insights into Cancer Pathogenesis
High-Throughput Genomic Profiling of Adult Solid Tumors Reveals Novel Insights into Cancer Pathogenesis
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DOI：
10.1158/0008-5472.can-16-2479
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发表时间：
2017-05-01
期刊：
影响因子：
11.2
通讯作者：
Lipson, Doron
中科院分区：
文献类型：
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作者：
Hartmaier, Ryan J.;Albacker, Lee A.;Lipson, Doron
基因组分析被广泛预测将成为临床肿瘤学的标准护理，但需要更有效的数据共享来加速精准医学的进展。在这里，我们描述了来自18，004种独特成人癌症的癌症相关基因组图谱。该数据集由162种肿瘤亚型组成，包括多种罕见和不常见肿瘤。将改变频率与癌症基因组图谱进行比较，发现了一些差异，并提示乳腺癌和肺癌队列中治疗难治性样本的富集。为了说明数据集中的新奇，我们调查了罕见疾病的基因组景观，并确定了与以前的研究相比，腺样囊性癌中NOTCH 1改变的频率增加。肿瘤抑制基因模式的分析揭示了某些基因的疾病特异性，但其他基因的广泛失活。我们发现了多种潜在的药物，新的和已知的激酶融合的疾病超出了他们目前公认的。对未知意义的变体的分析鉴定了SMAD 4改变在结肠癌中的富集和预测具有功能影响的其他罕见改变。对已确定的临床相关改变的分析突出了目前建议进行检测的分子变化谱，以及扩大获批靶向治疗适应症的机会。总体而言，该数据集提供了一种新的资源，可用于研究罕见的改变和疾病，验证临床相关性，并确定新的治疗靶点。(C)2017年AACR。
Genomic profiling is widely predicted to become a standard of care in clinical oncology, but more effective data sharing to accelerate progress in precision medicine will be required. Here, we describe cancer-associated genomic profiles from 18,004 unique adult cancers. The dataset was composed of 162 tumor subtypes including multiple rare and uncommon tumors. Comparison of alteration frequencies to The Cancer Genome Atlas identified some differences and suggested an enrichment of treatment-refractory samples in breast and lung cancer cohorts. To illustrate novelty within the dataset, we surveyed the genomic landscape of rare diseases and identified an increased frequency of NOTCH1 alterations in adenoid cystic carcinomas compared with previous studies. Analysis of tumor suppressor gene patterns revealed disease specificity for certain genes but broad inactivation of others. We identified multiple potentially druggable, novel and known kinase fusions in diseases beyond those in which they are currently recognized. Analysis of variants of unknown significance identified an enrichment of SMAD4 alterations in colon cancer and other rare alterations predicted to have functional impact. Analysis of established, clinically relevant alterations highlighted the spectrum of molecular changes for which testing is currently recommended, as well as opportunities for expansion of indications for use of approved targeted therapies. Overall, this dataset presents a new resource with which to investigate rare alterations and diseases, validate clinical relevance, and identify novel therapeutic targets. (C) 2017 AACR.