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Methylation Heterogeneity within Human Lung Carcinoids (LCs) Tumors

ABSTRACT: Methylation Heterogeneity within Human Lung Carcinoids (LCs) Tumors

PROVIDER: PRJNA484666 | ENA |

REPOSITORIES: ENA

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Methylation Heterogeneity within Human Lung Carcinoids (LCs) Tumors

Project description:DNA CpG methylation profiling of LC patients samples were performed to understand genotype to phenotype corrlelations , novel molecular subtypes and cell of origins Lung carcinoids (LCs) are rare and slow growing primary lung neoplasms that are understudied. Here, we performed targeted exome sequencing using a 354-cancer gene panel (n=29), mRNA sequencing (n=30) and DNA methylation assay (n=18) on macro-dissected lung carcinoids. The mutations we identified were enriched for genes involved in covalent histone modification/chromatin remodeling (34.5%) (MEN1, ARID1A, KMT2C and KMT2A were recurrently mutated) as well as DNA repair (17.2%) pathways. Unsupervised clustering and principle component analysis on gene expression and DNA methylation profiles showed 3 robust molecular subtypes (LC1, LC2, LC3) with distinct clinical features. MEN1 gene mutations were found to be enriched and exclusively in the LC2 subtype (p-value<0.001). The LC3 subtype is predominately found at endobronchial lung and earlier age of diagnosis. Immunohistochemical staining of two biomarkers, ASCL1 and S100, is sufficient to stratify the three subtypes. This molecular classification of lung carcinoids into three subtypes may help improve treatment decision and clinical management.

2019-07-01 | GSE118132 | GEO

Methylation Heterogeneity within Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

Project description:Methylation Heterogeneity within Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

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Transcriptomic profiling of human Lung Carcinoids (LCs)

Project description:Transcriptomic profiling of human Lung Carcinoids (LCs)

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Transcriptional Heterogeneity within the Glucocorticoid Response

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Structurally complex osteosarcoma genomes exhibit limited heterogeneity within individual tumors and across evolutionary time

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Structurally complex osteosarcoma genomes exhibit limited heterogeneity within individual tumors and across evolutionary time

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Deconstructive SCNT reveals heterogeneity within Treg population

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Heterogeneity within the PF-EPN-B subgroup

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Intra-Tumor DNA Methylation Heterogeneity in Glioblastoma; Implications for DNA Methylation-based Classification

Project description:Background: A feature of glioblastoma (GBM) is the cellular and molecular heterogeneity, both within and between tumors. This variability results in a risk for sampling bias and potential tumor escape from future targeted therapy. Heterogeneous gene expression within GBM is well documented, but little is known regarding the epigenetic heterogeneity. We therefore aimed to profile the intra-tumor DNA methylation heterogeneity in GBM. Methods: 3-4 biopsies per tumor from spatially separated regions were collected from 12 GBM patients. We performed genome-wide DNA methylation analysis (~850,000 CpG sites) and compared inter- and intra-tumor variation. Results: All samples were classified as GBM IDH wt or IDH mutated by DNA methylation profiling, but the GBM subtype differed within five tumors. Some GBM samples exhibited higher DNA methylation differences within tumors than between, and many CpG sites (mean: 17,000) had different methylation levels within the tumors. Conclusions: We demonstrated that intra-tumor DNA methylation heterogeneity is a feature of GBM. Although all biopsies were classified as GBM IDH wt/mutated by DNA methylation analysis, the assigned subtype differed in samples from the same patient. The observed DNA methylation heterogeneity within tumors is important to consider for methylation-based biomarkers and future improvements in stratification of GBM patients.

2019-02-27 | GSE116298 | GEO

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