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. 2026 Jan 2;136(1):e195809.
doi: 10.1172/JCI195809.

Germline inactivation of tumor suppressor BAP1 is associated with white spotting

Ching-Ni Njauw  1 , Zhenyu Ji  1 , David I Latoni  2 , Jose Mari Villa-Gonzalez  1   3 , Shelley McCormick  4 , Raj Kumar  5 , Dmitrii Usoltsev  6 , Mykyta Artomov  6 , Boyi Gan  7 , Hensin Tsao  1   4
Affiliations

Germline inactivation of tumor suppressor BAP1 is associated with white spotting

Ching-Ni Njauw et al. J Clin Invest. .

Abstract

Inherited BAP1 mutations cause melanoma and other cancers and can also lead to white hair patches or skin spots due to pigment cell loss.

Keywords: Dermatology; Genetic diseases; Genetics; Melanoma; Skin.

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Figures

Figure 1
Figure 1. BAP1 inactivation and pigmentation.
(A) Patient details and images of white spotting (demonstrated by Wood’s light in Cases 3,4,5,7). (B) Top genes correlated with BAP1 expression in normal human melanocytes (NHMs), the TCGA_SCKM and Lund cohorts, as ranked by Spearman coefficient, were subjected to Gene Ontology Biological Processes (GO-BP), GO-Cellular Compartment (GO-CC), and Human Phenotype Ontology (HPO) analysis; all GO and HPO analyses exhibited FDR < 0.05. (C) The 500 genes most correlated with BAP1 expression were subjected to HOMER analysis. Pigmentation-related transcription factors, MITF and TFE3, are highlighted in blue. (D) Suppression of Bap1 by sh(BAP1) in 3 melanoma cell lines leads to decreases in SOX10 and MITF, reduced cellular proliferation (Day 0 = 1; P values determined by t test on Day 5), and pigmentation loss. (E) Skin phenotypes of various Bap1 genotypes. Animal 1 (Bap1fl/fl) and Animal 2 (Tyr:CreA/Bap1fl/WT) have no visible phenotype. Animals 3–5 (Tyr:CreA/Bap1fl/fl) showed depigmentation of the fore- and hindpaws (red circles) while animals 4 and 5 had white spotting on the midabdomen. (F) Melanocyte quantitation (Sox10+ cells per hair follicle (HF)) shows significant reductions in the number of Sox10+ melanocytes (red arrows) in the depigmented abdominal area, ear, and dorsal paw of Tyr:CreA/Bap1fl/fl mouse compared with the Bap1fl/fl mouse (2-tailed t test).
See this image and copyright information in PMC

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