PMC

Significant affected genes and pathways in pulmonary carcinoids. (a) Significantly mutated genes and pathways identified by genome (n=29), exome (n=15) and transcriptome (n=69) sequencing. The percentage of pulmonary carcinoids with a specific gene or pathway mutated is noted at the right side. The q-values of the significantly mutated genes and pathways are shown in brackets (see Methods section). Samples are displayed as columns and arranged to emphasize mutually exclusive mutations. (b) Methylation levels of H3K9me3 and H3K27me3 in pulmonary carcinoids. Representative pictures of different degrees of methylation (high, intermediate, and low) for some of the samples summarized in . The mutated gene is shown in italics at the bottom right part of the correspondent picture. Wild-type samples are denoted by WT.

Expression data analysis of pulmonary carcinois based on RNAseq data. (a) Consensus Kmeans clustering^, using RNAseq expression data of 50 adenocarcinomas (AD, in blue), 42 small-cell lung cancer (SCLC, in red), and 69 pulmonary carcinoids (PCA, in purple) identified 3 groups using the clustering module from GenePattern and consensus CDF^, (left panel). The significance of the clustering was evaluated by using SigClust34 with a p<0.0001. Fisher's exact test35 was used to check associations between the clusters and the histological subtypes (right panel). (b) Gene Set Enrichment Analysis (GSEA) for SCLC versus PCA using RNAseq expression data. Low gene expression is indicated in blue and high expression, in red. On the right side are named the altered pathways in PCA (green) and SCLC (purple).

Genomic characterization of pulmonary carcinoids. (a) CIRCOS plot of the chromothripsis case. The outer ring shows chromosomes arranged end to end. Somatic copy number alterations (gains in red and losses in blue) detected by 6.0 SNP arrays are depicted in the inside ring. (b) Copy numbers and chimeric transcripts of affected chromosomes. Segmented copy number states (blue points) are shown together with raw copy number data averaged over 50 adjacent probes (grey points). To show the different levels of strength for the identified chimeric transcripts all curves are scaled according to the sequencing coverage at the fusion-point. (c) Mutation frequency detected by genome and exome sequencing in pulmonary carcinoids (PCA). Each blue dot represents the number of mutations per megabase in one pulmonary carcinoid sample. Average frequencies are also shown for adenocarcinomas (AD), squamous (SQ), and small-cell lung cancer (SCLC) base on previous studies^,, (d) Comparison of context independent transversion and transition rates (an overall strand symmetry is assumed) between rates derived from molecular evolution (evol), from a previous SCLC sequencing study, and from the pulmonary carcinoids (PCA) genome and exome sequencing. All rates are scaled as such that their overall sum is one.