Epigenetic Alterations and Tumor Mutational Burden in NSCLC
Posted: Monday, November 5, 2018
Research conducted by Liang-Liang Cai, MD, PhD, and colleagues at the Chinese Academy of Medical Sciences and Peking Union Medical College, indicates that DNA methylation seems to be associated with tumor mutational burden and may provide insight into treating and managing patients with non–small cell lung cancers (NSCLC). The study authors found 25 hypermethylated HOX genes that may serve as biomarkers for predicting tumor mutational burden. The study was presented at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC) in Toronto (Abstract MA06.07) and published in the Journal of Thoracic Oncology.
Using whole-exome sequencing, the authors surveyed the DNA landscape of 178 lung tissues (89 without any systemic therapy tumors and matched normal lung tissues). Of them, 104 were considered at a median level of tumor mutational burden and divided into low (57–79 range mutations per tumor) and high tumor mutational burden (252–465 range mutations per tumor) for analysis of the NSCLC methylome.
In patients with a high tumor mutational burden, the authors also observed more frequent aberrant DNA methylation, chromosomal amplifications and deletions, and mutational signatures. Both hyper- (76,938) and hypo- (217,203) methylation was reported in patients with cancer who had a high tumor mutational burden, whereas no cancer-specific epigenetic alterations were observed among those with lung cancer who had a low tumor mutational burden. Methylation sites covered 1,232 genes, including 25 HOX genes.
According to the authors, these study data suggest that DNA hypomethylation and TP53 mutation are associated with tumor mutational burden in NSCLC, and these biomarkers may contribute to improving precision management in this patient population.