Imperial College London
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PROFESSOR MIRIAM F. MOFFATT

Faculty of Medicine, National Heart & Lung Institute

Consul for the Faculty of Medicine, Professor
 
 
 
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Contact

 

+44 (0)20 7594 2942m.moffatt

 
 
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Location

 

400Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Domingo-Sabugo:2021:10.1101/2021.07.27.21260865,
author = {Domingo-Sabugo, C and Willis-Owen, SAG and Mandal, A and Nastase, A and Dwyer, S and Brambilla, C and Gálvez, JH and Zhuang, Q and Popat, S and Eveleigh, R and Munter, M and Lim, E and Nicholson, AG and Lathrop, M and Cookson, WOC and Moffatt, MF},
doi = {10.1101/2021.07.27.21260865},
title = {Distinct pancreatic and neuronal Lung Carcinoid molecular subtypes revealed by integrative omic analysis},
url = {http://dx.doi.org/10.1101/2021.07.27.21260865},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Summary</jats:title><jats:p>Lung Carcinoids (L-CDs) are uncommon low-grade neuroendocrine tumours that are only recently becoming characterised at the molecular level. Notably data on the molecular events that precipitate altered gene expression programmes are very limited. Here we have identified two discrete L-CD subtypes from transcriptomic and whole-genome DNA methylation data, and comprehensively defined their molecular profiles using Whole-Exome Sequencing (WES) and Single Nucleotide Polymorphism (SNP) genotyping. Subtype (Group) 1 features upregulation of neuronal markers (L-CD-NeU) and is characterised by focal spindle cell morphology, peripheral location (71%), high mutational load (<jats:italic>P</jats:italic>=3.4×10<jats:sup>−4</jats:sup>), recurrent copy number alterations and is enriched for Atypical Lung Carcinoids. Group 2 (L-CD-PanC) are centrally located and feature upregulation of pancreatic and metabolic pathway genes concordant with promoter hypomethylation of beta cell and genes related to insulin secretion (<jats:italic>P</jats:italic><1×10<jats:sup>−6</jats:sup>). L-CD-NeU tumours harbour mutations in chromatin remodelling and in SWI/SNF complex members, while L-CD-PanC tumours show aflatoxin mutational signatures and significant DNA methylation loss genome-wide, particularly enriched in repetitive elements (<jats:italic>P</jats:italic><2.2 × 10<jats:sup>−16</jats:sup>). Our findings provide novel insights into the distinct mechanisms of epigenetic dysregulation in these lung malignancies, potentially opening new avenues for biomarker selection and treatment in L-CD patients.</jats:p>
AU  - Domingo-Sabugo,C
AU  - Willis-Owen,SAG
AU  - Mandal,A
AU  - Nastase,A
AU  - Dwyer,S
AU  - Brambilla,C
AU  - Gálvez,JH
AU  - Zhuang,Q
AU  - Popat,S
AU  - Eveleigh,R
AU  - Munter,M
AU  - Lim,E
AU  - Nicholson,AG
AU  - Lathrop,M
AU  - Cookson,WOC
AU  - Moffatt,MF
DO  - 10.1101/2021.07.27.21260865
PY  - 2021///
TI  - Distinct pancreatic and neuronal Lung Carcinoid molecular subtypes revealed by integrative omic analysis
UR  - http://dx.doi.org/10.1101/2021.07.27.21260865
ER  -
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