title: TERT and AURKA gene copy number gains enhance the detection of acral lentiginous melanomas by fluorescence in situ hybridization.
abstract: The study of specific chromosomal loci through fluorescence in situ hybridization (FISH) is useful in differential diagnosis of melanocytic tumors. However, sensitivity rates vary, probably because of molecular heterogeneity. Acral lentiginous melanomas are characterized by copy number gains of small genomic regions, including CCND1, TERT, and AURKA. In a series of 58 acral melanocytic lesions, we explored the value of a four-color FISH probe, used in addition to determining MYC gene status, and assessed the potential diagnostic usefulness of newly developed probes targeting TERT and AURKA. Moreover, we tested CCND1, TERT, and AURKA protein expression by immunohistochemistry. The four-color FISH probe detected 85.3% of melanomas and 29.4% of TERT and AURKA copy number gains. Sensitivity was 97% (confidence interval 95%, 82.9% to 99.8%) for the combined results of all probes. No MYC copy number gains were detected. No nevi showed aberrations. Immunohistochemistry revealed a higher percentage of cells positive for CCND1, TERT, and AURKA protein in melanomas than in nevi (P ≤ 0.001). A significant correlation between gene copy number gain and protein expression was found for CCND1 (P = 0.015). Our results indicate that addition of specific FISH probes to the current probe could improve sensitivity for the diagnosis of acral melanomas. Further studies in larger numbers of cases are needed to validate these results.
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Diaz
authors.affiliation: Department of Biochemical and Molecular Genetics, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER), the Carlos III Institute of Health (ISCIII), Barcelona, Spain.
authors.forename: Joan Anton
authors.initials: JA
authors.lastname: Puig-Butillé
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Valera
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Concha
authors.initials: C
authors.lastname: Muñoz
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Costa
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Garcia-Herrera
authors.affiliation: Center for Biomedical Network Research on Rare Diseases (CIBERER), the Carlos III Institute of Health (ISCIII), Barcelona, Spain; Department of Dermatology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Carrera
authors.affiliation: Joseph Carreras Institute for Research against Leukemia, Hospital "Germans Trias i Pujol", Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Sole
authors.affiliation: Center for Biomedical Network Research on Rare Diseases (CIBERER), the Carlos III Institute of Health (ISCIII), Barcelona, Spain; Department of Dermatology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Malvehy
authors.affiliation: Center for Biomedical Network Research on Rare Diseases (CIBERER), the Carlos III Institute of Health (ISCIII), Barcelona, Spain; Department of Dermatology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain. Electronic address: lalos@clinic.ub.es.
authors.forename: Llucia
authors.initials: L
authors.lastname: Alos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064096:Aurora Kinase A / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D019098:Telomerase / Q000235:genetics*
chemical_list: D064096:Aurora Kinase A; D019098:Telomerase