title: Genetic profile of GNAQ-mutated blue melanocytic neoplasms reveals mutations in genes linked to genomic instability and the PI3K pathway.
abstract: Melanomas arising in association with a common or cellular blue nevus (MABN) comprise a relatively rare and heterogeneous group of lethal melanomas. Although GNAQ is known to be frequently mutated in common blue nevus, cellular blue nevus (CBN) and MABN and these malignant lesions present gross chromosome alterations harboring BAP1 mutations, little is known about other mutations that contribute to the development and progression of these neoplasms. Thus, the genetic profile of these tumors is important to increase the number of intervention and treatment modalities. Here, we characterized and genetically profiled two different sections of a rare MABN and two CBNs from three different patients. All of the samples harbored a GNAQ mutation, exhibited RAS pathway activation, and harbored additional mutations in genes associated with genomic instability and epigenetic regulation (KMT2C, FANCD2, ATR, ATRX, NBN, ERCC2, SETD2, and WHSC1). In addition, all neoplasms harbored mutations that directly or indirectly affected either the regulation or activation of the PI3K pathway (PIK3CA, NF1, INPP5B and GSK3B). Our results not only help understand the genetic complexity of these blue melanocytic lesions but provide a rationale to use the combination of PI3K/MTOR and MEK1/2 inhibitors against these types of tumors.
authors.affiliation: Biomedical Research in Melanoma-Animal Models and Cancer Laboratory, Oncology Program, Vall d'Hebron Research institute, VHIR-Vall d'Hebron Hospital, Barcelona-UAB 08035, Barcelona, Spain.
authors.forename: Mileidys
authors.initials: M
authors.lastname: Pérez-Alea
authors.affiliation: Cancer Genomics Group Translational Research Program, Vall d'Hebron Institute of Oncology-VHIO, Vall d'Hebron Hospital, Barcelona-UAB, Barcelona 08035, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vivancos
authors.affiliation: Cancer Genomics Group Translational Research Program, Vall d'Hebron Institute of Oncology-VHIO, Vall d'Hebron Hospital, Barcelona-UAB, Barcelona 08035, Spain.
authors.forename: Ginevra
authors.initials: G
authors.lastname: Caratú
authors.affiliation: Cancer Genomics Group Translational Research Program, Vall d'Hebron Institute of Oncology-VHIO, Vall d'Hebron Hospital, Barcelona-UAB, Barcelona 08035, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Matito
authors.affiliation: Biomedical Research in Melanoma-Animal Models and Cancer Laboratory, Oncology Program, Vall d'Hebron Research institute, VHIR-Vall d'Hebron Hospital, Barcelona-UAB 08035, Barcelona, Spain.|Anatomy Pathology Department, Vall d'Hebron Hospital, Barcelona-UAB, Barcelona 08035, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Ferrer
authors.affiliation: Anatomy Pathology Department, Vall d'Hebron Hospital, Barcelona-UAB, Barcelona 08035, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Hernandez-Losa
authors.affiliation: Clinical Oncology Program, Vall d'Hebron Institute of Oncology-VHIO, Vall d'Hebron Hospital, Barcelona-UAB, Barcelona 08035, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.affiliation: Biomedical Research in Melanoma-Animal Models and Cancer Laboratory, Oncology Program, Vall d'Hebron Research institute, VHIR-Vall d'Hebron Hospital, Barcelona-UAB 08035, Barcelona, Spain.|Clinical Oncology Program, Vall d'Hebron Institute of Oncology-VHIO, Vall d'Hebron Hospital, Barcelona-UAB, Barcelona 08035, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Muñoz
authors.affiliation: Biomedical Research in Melanoma-Animal Models and Cancer Laboratory, Oncology Program, Vall d'Hebron Research institute, VHIR-Vall d'Hebron Hospital, Barcelona-UAB 08035, Barcelona, Spain.|Dermatology Department, Vall d'Hebron Hospital, Barcelona-UAB, Barcelona 08035, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Garcia-Patos
authors.affiliation: Biomedical Research in Melanoma-Animal Models and Cancer Laboratory, Oncology Program, Vall d'Hebron Research institute, VHIR-Vall d'Hebron Hospital, Barcelona-UAB 08035, Barcelona, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Recio
mesh_terms: D004252:DNA Mutational Analysis; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D018329:Nevus, Blue / Q000235:genetics* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C554061:GNAQ protein, human; D019869:Phosphatidylinositol 3-Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: BAP1; GNAQ; blue nevus; genetic profile; melanoma