title: Hierarchical clustering of lung cancer cell lines using DNA methylation markers.
abstract: Recent analyses of global and gene-specific methylation patterns in cancer cells have suggested that cancers from different organs demonstrate distinct patterns of CpG island hypermethylation. Although certain CpG islands are frequently methylated in many different kinds of cancer, others are methylated only in specific tumor types. Because distinct patterns of CpG island hypermethylation can be seen in tumors from different organs, it seems likely that histological subtypes of cancer within a given organ may exhibit distinct methylation patterns as well. The goal of our study was to determine whether the patterns of CpG island hypermethylation could be used to distinguish between different histological subtypes of lung cancer. We analyzed the methylation status of 23 loci in 91 lung cancer cell lines using the quantitative real-time PCR method MethyLight. Genes PTGS2 (COX2), CALCA, MTHFR, ESR1, MGMT, MYOD1, and APC showed statistically significant differences in the level of CpG island methylation between small cell lung cancer (SCLC) and non-small cell lung cancer cell lines (NSCLC). Hierarchical clustering using a panel consisting of these seven loci yielded two major groups, one of which contained 78% of the SCLC lines. Within this group, a large cluster consisted almost exclusively of SCLC cell lines. Our results show that DNA methylation patterns differ between NSCLC and SCLC cell lines and suggest that these patterns could be developed into a powerful molecular marker to achieve accurate diagnosis of lung cancer.
authors.affiliation: Hamon Center for Therapeutic Oncology Research and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9593, USA.
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Virmani
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Tsou
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Siegmund
authors.forename: Linda Y C
authors.initials: LY
authors.lastname: Shen
authors.forename: Tiffany I
authors.initials: TI
authors.lastname: Long
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: Ite A
authors.initials: IA
authors.lastname: Laird-Offringa
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D005819:Genetic Markers