Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification

Abstract

Refined classification of LCLC has implications for diagnosis, prognostics, and therapy decisions. Our molecular analyses support the WHO 2015 classification of LCLC and LCNEC tumors, which herein follow different tumorigenic paths and can accordingly be stratified into different transcriptional subgroups, thus linking diagnostic immunohistochemical staining-driven classification with the transcriptional landscape of lung cancer.

New Insights into the Molecular Characteristics of Pulmonary Carcinoids and Large Cell Neuroendocrine Carcinomas, and the Impact on Their Clinical Management

“…Two studies extensively profiled carcinoids: Fernandez-Cuesta et al investigated 69 carcinoids by RNA sequencing (RNAseq) and 44 tumor-normal pairs by whole-genome sequencing or whole-exome sequencing (WES) ( Table 1). [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Simbolo et al used a discovery-screen approach that included profiling tumor-normal tissue samples from 14 carcinoids by WES and 23 tissue samples by targeted sequencing on 418 genes. 24 Armengol et al and Vollbrecht et al also analyzed a few cases using standard next-generation sequencing cancer panels (see Table 1).…”

“…The authors made some observations that led them to speculate about a possible link between the mutational groups and their transcriptional landscape; however, they acknowledged the limited number of LCNEC cases in the two mutational groups (11 versus three) and the need for larger studies to validate these results. 20 An overview of the molecular characteristics of LCNEC is provided in Figure 1, Table 3, and Supplementary File 1.…”

Gene Expression Profiling of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Transcriptomic Subtypes with Specific Genomic Alterations

“…8,13 Gene expression profiles produce a global picture of cellular function, and it has been shown that the transcriptional phenotypes of lung cancers mimic the WHO classification. 6,14 They may also provide additional stratification within histological subtypes (that is, the potential to identify molecular subgroups within tumors showing similar morphological features). 14,15 Three gene expression profiling studies of LNETs have been recently published.…”

An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1–Positive Lung Adenocarcinomas

“…Within these morphologically defined entities, extensive molecular studies revealed highly heterogeneous features with respect to genomic alterations and transcriptional profiles. [2][3][4][5] In the recent WHO classification system, SCLC and largecell neuroendocrine carcinoma (LCNEC) are grouped into high-grade neuroendocrine tumors. 6 These tumors show neuroendocrine morphology and are immunostained for neuroendocrine markers, neural cell adhesion molecule 1 (NCAM1), synaptophysin (SYP), and/or chromogranin A (CHGA).…”