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| Status |
Public on Sep 16, 2023 |
| Title |
Genome-Wide Epigenomic Profiling of Primary Non-Small Cell Lung Cancer Reveals Specific and Recurrent DNA Methylation Alterations in Smoker Versus Never-Smoker Patients |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment. To better understand the potential contribution of DNA methylation alterations to tumor phenotype in non-small cell lung cancer (NSCLC) in both smoker and never-smoker patients, we performed a comprehensive, genome-wide profiling of DNA methylation in 17 primary non-small cell lung cancer and 10 matched normal lung samples using the complementary methylation assays MeDIP-seq and MRE-seq. Compared to patient-matched non-malignant lung tissue, we report recurrent methylation changes of several gene promoters, many previously implicated in cancer, including FAM83A and SEPT9 (hypomethylation), and PCDH7, NKX2-1, and SOX17 (hypermethylation). Although smoker and never-smoker patients shared many methylation changes, several were specific and recurrent within a particular smoking status. In particular, never-smokers displayed a greater proportion of hypoDMRs and exhibited a greater number of recurrently hypomethylated promoters, including the promoter of the oncogene ASPSCR1, and others previously linked to cancer, including TOP2A, DPP9, and USP39. Methylation changes outside of promoters were also widespread and often recurrent, particularly the loss of methylation over repetitive elements, highly enriched for ERV1 subfamilies. Recurrent hypoDMRs were also enriched for several transcription factor (TF) binding motifs, often for genes involved in signaling and cell proliferation, including 71% encoding a binding site of NKX2-1, which was found to be significantly upregulated in TCGA LUAD samples. Furthermore, the overwhelming majority of DMRs identified in this study were found to reside in an active chromatin state in at least one tissue profiled using the Roadmap Epigenome data, suggesting that methylation changes may contribute to altered regulatory programs through the adaptation of cell type-specific expression programs.
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| Overall design |
We performed methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation sensitive restriction enzyme sequencing (MRE-seq), which profile methylated and unmethyalted CpG sites, respecitvely, for 17 lung adenocarcinoma tumors and 10 matched normal lung samples. MeDIP-seq and MRE-seq data were integrated using the M&M algorithm to identify regions differentially methylated between two samples, and were also integrated using methylCRF to calculate methylation value across indivual CpGs for each sample.
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| Contributor(s) |
Karlow JA, Pehrsson EC, Xing X, Watson M, Devarakonda S, Govindan R, Wang T |
| Citation(s) |
37742993 |
| Submission date |
Aug 10, 2022 |
| Last update date |
Jan 08, 2024 |
| Contact name |
Ting Wang |
| E-mail(s) |
twang@wustl.edu
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| Phone |
(314) 286-0865
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| Organization name |
Washington University in St. Louis
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| Department |
Genetics
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| Street address |
4515 McKinley Ave
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| City |
St. Louis |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (56)
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| GSM6443309 |
Patient 2385, Normal lung, Unconfirmed smoking status, smoL1, MeDIP |
| GSM6443310 |
Patient 2385, Normal lung, Unconfirmed smoking status, smoL1, MRE |
| GSM6443311 |
Patient 2385, Lung tumor, Unconfirmed smoking status, smoL26, MeDIP |
| GSM6443312 |
Patient 2385, Lung tumor, Unconfirmed smoking status, smoL26, MRE |
| GSM6443313 |
Patient 2422, Lung tumor, Former smoker, smoL2, MeDIP |
| GSM6443314 |
Patient 2422, Lung tumor, Former smoker, smoL2, MRE |
| GSM6443315 |
Patient 4796, Normal lung, Unconfirmed smoking status, smoL15, MeDIP |
| GSM6443316 |
Patient 4796, Normal lung, Unconfirmed smoking status, smoL15, MRE |
| GSM6443317 |
Patient 4796, Lung tumor, Unconfirmed smoking status, smoL7, MeDIP |
| GSM6443318 |
Patient 4796, Lung tumor, Unconfirmed smoking status, smoL7, MRE |
| GSM6443319 |
Patient 4999, Normal lung, Smoker, smoL17, MeDIP |
| GSM6443320 |
Patient 4999, Normal lung, Smoker, smoL17, MRE |
| GSM6443321 |
Patient 4999, Lung tumor, Smoker, smoL3, MeDIP |
| GSM6443322 |
Patient 4999, Lung tumor, Smoker, smoL3, MRE |
| GSM6443323 |
Patient 6130, Lung tumor, Smoker, smoL5, MeDIP |
| GSM6443324 |
Patient 6130, Lung tumor, Smoker, smoL5, MRE |
| GSM6443325 |
Patient 6339, Normal lung, Unconfirmed smoking status, smoL25, MeDIP |
| GSM6443326 |
Patient 6339, Normal lung, Unconfirmed smoking status, smoL25, MRE |
| GSM6443327 |
Patient 6339, Lung tumor, Unconfirmed smoking status, smoL6, MeDIP |
| GSM6443328 |
Patient 6339, Lung tumor, Unconfirmed smoking status, smoL6, MRE |
| GSM6443329 |
Patient 6356, Normal lung, Unconfirmed smoking status, smoL18, MeDIP |
| GSM6443330 |
Patient 6356, Normal lung, Unconfirmed smoking status, smoL18, MRE |
| GSM6443331 |
Patient 6356, Lung tumor, Unconfirmed smoking status, smoL21, MeDIP |
| GSM6443332 |
Patient 6356, Lung tumor, Unconfirmed smoking status, smoL21, MRE |
| GSM6443333 |
Patient 6503, Normal lung, Smoker, smoL27, MeDIP |
| GSM6443334 |
Patient 6503, Normal lung, Smoker, smoL27, MRE |
| GSM6443335 |
Patient 6503, Lung tumor, Smoker, smoL24, MeDIP |
| GSM6443336 |
Patient 6503, Lung tumor, Smoker, smoL24, MRE |
| GSM6443337 |
Patient 8666, Normal lung, Never-smoker, smoL16, MeDIP |
| GSM6443338 |
Patient 8666, Normal lung, Never-smoker, smoL16, MRE |
| GSM6443339 |
Patient 8666, Lung tumor, Never-smoker, smoL11, MeDIP |
| GSM6443340 |
Patient 8666, Lung tumor, Never-smoker, smoL11, MRE |
| GSM6443341 |
Patient 8868, Lung tumor, Smoker, smoL9, MeDIP |
| GSM6443342 |
Patient 8868, Lung tumor, Smoker, smoL9, MRE |
| GSM6443343 |
Patient 8951, Normal lung, Never-smoker, smoL23, MeDIP |
| GSM6443344 |
Patient 8951, Normal lung, Never-smoker, smoL23, MRE |
| GSM6443345 |
Patient 8951, Lung tumor, Never-smoker, smoL12, MeDIP |
| GSM6443346 |
Patient 8951, Lung tumor, Never-smoker, smoL12, MRE |
| GSM6443347 |
Patient 9890, Normal lung, Smoker, smoL14, MeDIP |
| GSM6443348 |
Patient 9890, Normal lung, Smoker, smoL14, MRE |
| GSM6443349 |
Patient 9890, Lung tumor, Smoker, smoL4, MeDIP |
| GSM6443350 |
Patient 9890, Lung tumor, Smoker, smoL4, MRE |
| GSM6443351 |
Patient 9975, Normal lung, Smoker, smoL20, MeDIP |
| GSM6443352 |
Patient 9975, Normal lung, Smoker, smoL20, MRE |
| GSM6443353 |
Patient 9975, Lung tumor, Smoker, smoL13, MeDIP |
| GSM6443354 |
Patient 9975, Lung tumor, Smoker, smoL13, MRE |
| GSM6443355 |
Patient 11266, Normal lung, Smoker, smoL28, MeDIP |
| GSM6443356 |
Patient 11266, Normal lung, Smoker, smoL28, MRE |
| GSM6443357 |
Patient 11266, Lung tumor, Smoker, smoL8, MeDIP |
| GSM6443358 |
Patient 11266, Lung tumor, Smoker, smoL8, MRE |
| GSM6443359 |
Patient 11584, Lung tumor, Smoker, smoL10, MeDIP |
| GSM6443360 |
Patient 11584, Lung tumor, Smoker, smoL10, MRE |
| GSM6443361 |
Patient 11732, Lung tumor, Unconfirmed smoking status, smoL22, MeDIP |
| GSM6443362 |
Patient 11732, Lung tumor, Unconfirmed smoking status, smoL22, MRE |
| GSM6443363 |
Patient 14658, Lung tumor, Never-smoker, smoL19, MeDIP |
| GSM6443364 |
Patient 14658, Lung tumor, Never-smoker, smoL19, MRE |
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| Relations |
| BioProject |
PRJNA868383 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE210957_DMRs_qv_Patient_processed_data.tar.gz |
2.0 Mb |
(ftp)(http) |
TAR |
| GSE210957_smoL_processed_data.tar.gz |
4.9 Gb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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