title: Kinase gene fusions in defined subsets of melanoma.
abstract: Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by Immunohistochemistry (IHC) or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought and should be further explored particularly in melanomas lacking known driver mutations.
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Turner
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Kasey
authors.initials: K
authors.lastname: Couts
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Sheren
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Siriwimon
authors.initials: S
authors.lastname: Saichaemchan
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Witthawat
authors.initials: W
authors.lastname: Ariyawutyakorn
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Izabela
authors.initials: I
authors.lastname: Avolio
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Cabral
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Magdelena
authors.initials: M
authors.lastname: Glogowska
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Amato
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Robinson
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hintzsche
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Applegate
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Seelenfreund
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Wells
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Bagby
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: John
authors.initials: J
authors.lastname: Tentler
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Aik-Choon
authors.initials: AC
authors.lastname: Tan
authors.affiliation: Department of Pathology, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Wisell
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: William
authors.initials: W
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051186:Armadillo Domain Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008545:Melanoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
chemical_list: D051186:Armadillo Domain Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C062333:ROS1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: acral; kinase; melanoma; pan-negative; rearrangement