title: Phenotypic characterization of nevus and tumor patterns in MITF E318K mutation carrier melanoma patients.
abstract: A germline polymorphism of the microphthalmia transcription factor (MITF) gene encoding a SUMOylation-deficient E318K-mutated protein has recently been described as a medium-penetrance melanoma gene. In a clinical assessment of nevi from 301 volunteers taken from Queensland, we identified six individuals as MITF E318K mutation carriers. The phenotype for 5 of these individuals showed a commonality of fair skin, body freckling that varied over a wide range, and total nevus count between 46 and 430; in addition, all were multiple primary melanoma patients. The predominant dermoscopic signature pattern of nevi was reticular, and the frequency of globular nevi in carriers varied, which does not suggest that the MITF E318K mutation acts to force the continuous growth of nevi. Excised melanocytic lesions were available for four MITF E318K carrier patients and were compared with a matched range of wild-type (WT) melanocytic lesions. The MITF staining pattern showed a predominant nuclear signal in all sections, with no significant difference in the nuclear/cytoplasmic ratio between mutation-positive or -negative samples. A high incidence of amelanotic melanomas was found within the group, with three of the five melanomas from one patient suggesting a genetic interaction between the MITF E318K allele and an MC1R homozygous red hair color (RHC) variant genotype.
authors.affiliation: Melanogenix Group, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. Electronic address: r.sturm@imb.uq.edu.au.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sturm
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Carly
authors.initials: C
authors.lastname: Fox
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: Phil
authors.initials: P
authors.lastname: McClenahan
authors.affiliation: Melanogenix Group, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Kasturee
authors.initials: K
authors.lastname: Jagirdar
authors.affiliation: Melanogenix Group, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia; Department of Haematology and Medical Oncology, Fundacion Investigacion Hospital Clinico-INCLIVA, Valencia, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Ibarrola-Villava
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Department of Dermatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Banan
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Department of Dermatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Abbott
authors.affiliation: Department of Haematology and Medical Oncology, Fundacion Investigacion Hospital Clinico-INCLIVA, Valencia, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Gabrielli
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Department of Dermatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Peter Soyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006200:Hair Color / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D008875:Middle Aged; D009506:Nevus / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor