Lung Cancer: Lung Cancer III |

Targeted DNA Methylation Analysis Explores Association of Adenocarcinoma and Neuroendocrine Epitypes With Lung Cancer FREE TO VIEW

Jing Liu, PhD
Author and Funding Information

The Second Hospital of Jilin University, Changchun, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A320. doi:10.1016/j.chest.2016.02.333
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: DNA methylation analysis is the most frequently used method to explore the major mechanism of gene expression regulation which is one of the most responsible factors for the promotion of tumorigenesis. The association of DNA methylation patterns based on clinically relevant subgroups with lung cancer is still unexplored and not clear.

METHODS: Performed a targeted DNA methylation analysis of whole genome using 450 K Illumina BeadArrays on 146 tumor cells and 15 normal lung tissues. A total of 92 adenocarcinomas, 2 adenosquamous cancer, 30 squamous-cell carcinomas, 7 large-cell carcinomas, 4 small-cell lung carcinomas, and 11 large-cell neuroendocrine carcinomas have contributed to the 146 lung cancer tissues. In order to identify DNA methylation subgroups, unsupervised bootstrap clustering was performed. Subgroups were validated in 135 squamouscell carcinomas and 712 adenocarcinomas followed by their characterization through gene expression profiles, clinicopathologic factors and whole-exome sequencing data.

RESULTS: Our analysis has revealed five epitypes (also said as DNA methylation subgroups). Among these five epitypes, four had shown quite an association between supervised and unsupervised gene expression phenotypes along with their differences in genomic instability, global hypomethylation, expression of proliferation-associated genes and promoter hypermethylation, and KRAS and EGFR mutations, while the one remaining epitype had a distinct association with small-cell and large-cell neuroendocrine carcinomas.

CONCLUSIONS: We found a strong association of adenocarcinoma and neuroendocrine epitypes with molecular and clinicopathologic characteristics of lung cancer patients.

CLINICAL IMPLICATIONS: In this way we see a possibility of a more accurate classification of lung cancer and tailored patient therapy.

DISCLOSURE: The following authors have nothing to disclose: Jing Liu

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