Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors

Study ID Alternative Stable ID Type
EGAS00001000708 Other

Study Description

Large-cell neuroendocrine lung carcinomas (LCNEC) have similarities with other lung cancers, but their precise relationship has remained unclear. We conducted comprehensive genomic (n=60) and transcriptomic (n=69) analyses of 75 LCNECs and identified two molecular subgroups: “type I LCNECs” with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and “type II LCNECs” enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/NOTCHhigh and upregulation of immune-related pathways. In conclusion, LCNECs are comprised of two molecularly defined subgroups, and distinguishing them from SCLC may allow for stratified targeted ... (Show More)

Study Datasets 4 datasets.

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Dataset ID Description Technology Samples
WGS dataset LCNEC study
Illumina HiSeq 2000 11
RNAseq Data set
Illumina HiSeq 2000 40
Whole exome sequencing
Illumina HiSeq 2000 48
SNP 6.0 arrays of LCNEC samples
Affymetrix SNP 6.0 54

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