title: Genetic evolution of nevus of Ota reveals clonal heterogeneity acquiring BAP1 and TP53 mutations.
abstract: Melanoma presents molecular alterations based on its anatomical location and exposure to environmental factors. Due to its intrinsic genetic heterogeneity, a simple snapshot of a tumor's genetic alterations does not reflect the tumor clonal complexity or specific gene-gene cooperation. Here, we studied the genetic alterations and clonal evolution of a unique patient with a Nevus of Ota that developed into a recurring uveal-like dermal melanoma. The Nevus of Ota and ulterior lesions contained GNAQ mutations were c-KIT positive, and tumors showed an increased RAS pathway activity during progression. Whole-exome sequencing of these lesions revealed the acquisition of BAP1 and TP53 mutations during tumor evolution, thereby unmasking clonal heterogeneity and allowing the identification of cooperating genes within the same tumor. Our results highlight the importance of studying tumor genetic evolution to identify cooperating mechanisms and delineate effective therapies.
authors.affiliation: Cancer Genomics Group Translational Research Program, Vall dHebron Institute of Oncology-VHIO, Vall dHebron Hospital, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vivancos
authors.affiliation: Cancer Genomics Group Translational Research Program, Vall dHebron Institute of Oncology-VHIO, Vall dHebron Hospital, Barcelona, Spain.
authors.forename: Ginevra
authors.initials: G
authors.lastname: Caratú
authors.affiliation: Cancer Genomics Group Translational Research Program, Vall dHebron Institute of Oncology-VHIO, Vall dHebron Hospital, Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Matito
authors.affiliation: Clinical Oncology Program, Vall dHebron Hospital, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Muñoz
authors.affiliation: Anatomy Pathology Department, Vall dHebron Hospital, Barcelona, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Ferrer
authors.affiliation: Anatomy Pathology Department, Vall dHebron Hospital, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Hernández-Losa
authors.affiliation: Dermatology Department, Vall dHebron Hospital, Barcelona, Spain.
authors.forename: Domingo
authors.initials: D
authors.lastname: Bodet
authors.affiliation: Biomedical Research in Melanoma-Animal Models and Cancer Laboratory, Vall dHebron Research Institute-VHIR Vall d'Hebron Hospital, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Mileidys
authors.initials: M
authors.lastname: Pérez-Alea
authors.affiliation: Clinical Oncology Program, Vall dHebron Hospital, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.affiliation: Dermatology Department, Vall dHebron Hospital, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Garcia-Patos
authors.affiliation: Biomedical Research in Melanoma-Animal Models and Cancer Laboratory, Vall dHebron Research Institute-VHIR Vall d'Hebron Hospital, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Recio
mesh_terms: D000328:Adult; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009507:Nevus of Ota / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; C554061:GNAQ protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: BAP1; GNAQ; Nevus Ota; genetic evolution; melanoma heterogeneity