title: Discovery and development of DNA methylation-based biomarkers for lung cancer.
abstract: Lung cancer remains the primary cause of cancer-related deaths worldwide. Improved tools for early detection and therapeutic stratification would be expected to increase the survival rate for this disease. Alterations in the molecular pathways that drive lung cancer, which include epigenetic modifications, may provide biomarkers to help address this major unmet clinical need. Epigenetic changes, which are defined as heritable changes in gene expression that do not alter the primary DNA sequence, are one of the hallmarks of cancer, and prevalent in all types of cancer. These modifications represent a rich source of biomarkers that have the potential to be implemented in clinical practice. This perspective describes recent advances in the discovery of epigenetic biomarkers in lung cancer, specifically those that result in the methylation of DNA at CpG sites. We discuss one approach for methylation-based biomarker assay development that describes the discovery at a genome-scale level, which addresses some of the practical considerations for design of assays that can be implemented in the clinic. We emphasize that an integrated technological approach will enable the development of clinically useful DNA methylation-based biomarker assays. While this article focuses on current literature and primary research findings in lung cancer, the principles we describe here apply to the discovery and development of epigenetic biomarkers for other types of cancer.
authors.affiliation: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Walter
authors.forename: Thomas
authors.initials: T
authors.lastname: Holcomb
authors.forename: Tom
authors.initials: T
authors.lastname: Januario
authors.forename: Robert L
authors.initials: RL
authors.lastname: Yauch
authors.forename: Pan
authors.initials: P
authors.lastname: Du
authors.forename: Richard
authors.initials: R
authors.lastname: Bourgon
authors.forename: Somasekar
authors.initials: S
authors.lastname: Seshagiri
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Amler
authors.forename: Garret M
authors.initials: GM
authors.lastname: Hampton
authors.forename: David
authors.initials: D
authors.lastname: S Shames
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000295:instrumentation / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D057166:High-Throughput Screening Assays; D006657:Histones / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D022661:RNA, Untranslated / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D022661:RNA, Untranslated