BibTex format
@article{Domingo-Sabugo:2024:10.1002/path.6352,
author = {Domingo-Sabugo, C and Willis-Owen, SA 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, GM and Cookson, WO and Moffatt, MF},
doi = {10.1002/path.6352},
journal = {J Pathol},
title = {Genomic analysis defines distinct pancreatic and neuronal subtypes of lung carcinoid.},
url = {http://dx.doi.org/10.1002/path.6352},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Lung carcinoids (L-CDs) are rare, poorly characterised neuroendocrine tumours (NETs). L-CDs are more common in women and are not the consequence of cigarette smoking. They are classified histologically as typical carcinoids (TCs) or atypical carcinoids (ACs). ACs confer a worse survival. Histological classification is imperfect, and there is increasing interest in molecular markers. We therefore investigated global transcriptomic and epigenomic profiles of 15 L-CDs resected with curative intent at Royal Brompton Hospital. We identified underlying mutations and structural abnormalities through whole-exome sequencing (WES) and single nucleotide polymorphism (SNP) genotyping. Transcriptomic clustering algorithms identified two distinct L-CD subtypes. These showed similarities either to pancreatic or neuroendocrine tumours at other sites and so were named respectively L-CD-PanC and L-CD-NeU. L-CD-PanC tumours featured upregulation of pancreatic and metabolic pathway genes matched by promoter hypomethylation of genes for beta cells and insulin secretion (p < 1 × 10-6). These tumours were centrally located and showed mutational signatures of activation-induced deaminase/apolipoprotein B editing complex activity, together with genome-wide DNA methylation loss enriched in repetitive elements (p = 2.2 × 10-16). By contrast, the L-CD-NeU group exhibited upregulation of neuronal markers (adjusted p < 0.01) and was characterised by focal spindle cell morphology (p = 0.04), peripheral location (p = 0.01), high mutational load (p = 2.17 × 10-4), recurrent copy number alterations, and enrichment for ACs. Mutations affected chromatin remodelling and SWI/SNF complex pathways. L-CD-NeU tumours carried a mutational signature attributable to aflatoxin and aristolochic acid (p = 0.05), suggesting a possible environmenta
AU - Domingo-Sabugo,C
AU - Willis-Owen,SA
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,GM
AU - Cookson,WO
AU - Moffatt,MF
DO - 10.1002/path.6352
PY - 2024///
TI - Genomic analysis defines distinct pancreatic and neuronal subtypes of lung carcinoid.
T2 - J Pathol
UR - http://dx.doi.org/10.1002/path.6352
UR - https://www.ncbi.nlm.nih.gov/pubmed/39329437
ER -