Fig. 2

Figure 2. DENND5A is variably expressed in familial melanomas and enriched in pigmented melanoma tissue. A. Western blotting of DENND5A protein expression in tumors from familial melanomas from a Karolinska University Hospital–based registry since 2000. B. Quantification of relative DENND5A protein expression. Red dot represents DENND5A protein expression in melanoma (sample 355) derived from heterozygote individual (II:1). A dotted line is drawn across the DENND5A heterozygote sample as reference for potential DENND5A suppression. C. DENND5A mRNA expression in the skin cutaneous melanoma (SKCM) cohort of The Cancer Genome Atlas (TCGA) is classified into “normal-like” and “pigmentation” subtype by applying pigmentation gene signature and then compared. D-F. ST analysis on a CMM. D. Hematoxylin and Eosin stained CMM section (left) and higher magnification showing the pigmentation from the section (right). Scale bar: 1 cm (left), 0.25 cm (right). E. ST microarray on CMM section with barcoded spots of 100 mm diameter and 200 mm center-to-center distance. F. Density plot of DENND5A expression ran by trendsceek in the same section, with the regions of significantly elevated DENND5A expression marked red. G. Matrix of UV-related alterations (CC>TT in red; dpC>T, C>T transition at dipyrimidines, in pink) from all TCGA SKCMs, arising from both chronic (CSD) and nonchronic (non-CSD) sun-exposed body sites (n = 38). Sample types (primary or metastatic), body sites (CSD or non-CSD), and detected DENND5A somatic variants are color-coded and then sorted after DENND5A mRNA expression. H. Proportion of UV signature (CC>TT transitions) from DENND5A^High (highest 15) and DENND5A^Low (lowest 15) mRNA compared and shown as mean ± SEM. C., H. two-tailed, unpaired t test. CMM, cutaneous malignant melanoma; CSD, chronically sun damaged; ST, spatial transcriptomic. ∗P <.05; ∗∗∗P <.001.