Genomic and Transcriptomic Profiling of Brain Metastases

Cancers

Christopher P. Wardell¹  Analiz Rodriguez¹  Madison P. Lee²  Annick De Loose²  Murat Gokden³  Alan J. Tackett⁴  Issam Makhoul⁴  Emilie Darrigues⁴ 

[1] Department of Biomedical Informatics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA;Department of Neurosurgery, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA;Department of Pathology, 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;

关键词: bioinformatics;    genomics;    transcriptomics;    brain metastases;   

DOI  :  10.3390/cancers13225598

来源: DOAJ

【 摘 要 】

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 (p < 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.

【 授权许可】

Unknown