Wardell Christopher P, Darrigues Emilie, De Loose Annick, Lee Madison P, Gokden Murat, Makhoul Issam, Tackett Alan J, Rodriguez Analiz
Department of Biomedical Informatics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA.
Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA.
Cancers (Basel). 2021 Nov 9;13(22):5598. doi: 10.3390/cancers13225598.
Brain metastases (BM) are the most common brain tumors in adults occurring in up to 40% of all cancer patients. Multi-omics approaches allow for understanding molecular mechanisms and identification of markers with prognostic significance. In this study, we profile 130 BM using genomics and transcriptomics and correlate molecular characteristics to clinical parameters. The most common tumor origins for BM were lung (40%) followed by melanoma (21%) and breast (15%). Melanoma and lung BMs contained more deleterious mutations than other subtypes ( < 0.001). Mutational signatures suggested that the bulk of the mutations were gained before metastasis. A novel copy number event centered around the MCL1 gene was found in 75% of all samples, suggesting a broader role in promoting metastasis. Unsupervised hierarchical cluster analysis of transcriptional signatures available in 65 samples based on the hallmarks of cancer revealed four distinct clusters. Melanoma samples formed a distinctive cluster in comparison to other BM subtypes. Characteristics of molecular profiles did not correlate with survival. However, patients with self-identified black race or those who did not receive radiation correlated with poor survival. These data identify potential new drivers of brain metastatic progression. Our data also suggest further investigation of sociodemographic and clinical features is needed in BM cohorts.
脑转移瘤（BM）是成人中最常见的脑肿瘤，在所有癌症患者中发生率高达40%。多组学方法有助于理解分子机制并识别具有预后意义的标志物。在本研究中，我们对130例脑转移瘤进行了基因组学和转录组学分析，并将分子特征与临床参数相关联。脑转移瘤最常见的肿瘤起源是肺癌（40%），其次是黑色素瘤（21%）和乳腺癌（15%）。黑色素瘤和肺癌脑转移瘤比其他亚型含有更多有害突变（<0.001）。突变特征表明，大部分突变是在转移前获得的。在所有样本的75%中发现了一个以MCL1基因为中心的新拷贝数事件，提示其在促进转移中发挥更广泛的作用。基于癌症特征对65个样本中可用的转录特征进行无监督层次聚类分析，发现了四个不同的聚类。与其他脑转移瘤亚型相比，黑色素瘤样本形成了一个独特的聚类。分子谱特征与生存率无关。然而，自我认定为黑人种族的患者或未接受放疗的患者生存率较差。这些数据确定了脑转移进展的潜在新驱动因素。我们的数据还表明，需要在脑转移瘤队列中进一步研究社会人口统计学和临床特征。
