Integrative genomic characterization identifies molecular subtypes of lung carcinoids Journal Article
| Authors: | Laddha, S. V.; da Silva, E. M.; Robzyk, K.; Untch, B. R.; Ke, H.; Rekhtman, N.; Poirier, J. T.; Travis, W. D.; Tang, L. H.; Chan, C. S. |
| Article Title: | Integrative genomic characterization identifies molecular subtypes of lung carcinoids |
| Abstract: | Lung carcinoids (LC) are rare and slow growing primary lung neuroendocrine tumors. We performed targeted exome sequencing, mRNA sequencing, and DNA methylation array analysis on macro-dissected LCs. Recurrent mutations were enriched for genes involved in covalent histone modification/ chromatin remodeling (34.5%; MEN1, ARID1A, KMT2C, and KMT2A) as well as DNA repair (17.2%) pathways. Unsupervised clustering and principle component analysis on gene expression and DNA methylation profiles showed three robust molecular subtypes (LC1, LC2, LC3) with distinct clinical features. MEN1 gene mutations were found to be exclusively enriched in the LC2 subtype. LC1 and LC3 subtypes were predominately found at peripheral and endobronchial lung, respectively. The LC3 subtype was diagnosed at a younger age than LC1 and LC2 subtypes. IHC staining of two biomarkers, ASCL1 and S100, sufficiently stratified the three subtypes. This molecular classification of LCs into three subtypes may facilitate understanding of their molecular mechanisms and improve diagnosis and clinical management. © 2019 American Association for Cancer Research. |
| Journal Title: | Cancer Research |
| Volume: | 79 |
| Issue: | 17 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2019-09-01 |
| Start Page: | 4339 |
| End Page: | 4347 |
| Language: | English |
| DOI: | 10.1158/0008-5472.Can-19-0214 |
| PUBMED: | 31300474 |
| PROVIDER: | scopus |
| PMCID: | PMC6733269 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2019 -- Source: Scopus |
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