Fig. 7: Multifocal and unifocal forms belong to two different pathologies. | Nature Communications

Fig. 7: Multifocal and unifocal forms belong to two different pathologies.

From: Comprehensive molecular portrait reveals genetic diversity and distinct molecular subtypes of small intestinal neuroendocrine tumors

Fig. 7

Omics can define unifocal vs multifocal forms of siNETs a Venn-diagram of somatic point mutations and small indels on the whole-genome scale for available WGS samples of multifocal patients P101, P17, P41 and P68 (patient P68 was analyzed using a tumor as a paired sample). b Volcano plot for multifocal (n = 45) vs unifocal (n = 57) differential gene expression (DE) analysis; p-values are indicated on the y-axis (two-tailed Wald test with Benjamini-Hochberg correction). c Hierarchical clustering based on the 9 highly significantly differentially expressed coding genes ( | log2(FoldChange)|>1 & pval.adj < 1e-2). ATP8B3 (ATPase Phospholipid Transporting 8B3); CAMKK1 (Calcium/Calmodulin Dependent Protein Kinase Kinase 1); HOXC10 (Homeobox C10); LIPF (Lipase F, Gastric Type); NCR1 (Natural Cytotoxicity Triggering Receptor 1); NWD2 (NACHT And WD Repeat Domain Containing 2); PIK3C2G (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Gamma); PLA2G2C (Phospholipase A2 Group IIC); SEMA3E (Semaphorin 3E). d Volcano plot for multifocal (n = 44) vs unifocal (n = 54) differential methylation (DM) analysis; p-values are indicated on the y-axis (two-tailed T-test with Benjamini-Hochberg correction). e Hierarchical clustering based on the 836 significantly differentially methylated probes (delta(Beta)>10%, pval.adj < 5e-2). f Multifocal (n = 45) vs unifocal (n = 57) boxplots of gene expression for endocrine hormones or converting enzymes (log2TPM). GAST (Gastrin); GCG (Pro-glucagon: Glucagon-like peptide 1 et 2, Oxyntomodulin); GIP (Gastric inhibitory polypeptide); HDC (Histidine decarboxylase); NTS (Neurotensin); SST (Somatostatin). Boxplots: center line = median, box range 25th–75th percentile, minimum/maximum denoted by whiskers. Significance was determined by Mann-Whitney U tests. Clustering method: Ward’s; distance: Spearman. Recapitulative ssGSEA score of each gene cluster (epithelial, vesicular, mesenchymal and immune), chr18.del and chr4.10.14.gains statuses together with methylation subtypes are indicated as bottom annotations. FGA (Fraction genome altered); TPM (Transcripts Per Million).

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