Giant congenital melanocytic nevus with vascular malformation and epidermal cysts associated with a somatic activating mutation in BRAF

Autor: Frédéric Fina, Helmuth Vorbringer, Christian Rose, Pauline Heux, Benjamin Schwarz, Nicolas Macagno, Birgit Kahle, Stéphane Zaffran, Sven Krengel, Irina Berger, Heather C. Etchevers
Přispěvatelé: Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Lille - Faculté de Médecine, Maïeutique, Sciences de la santé (FMMS), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Universitätsklinikum Schleswig-Holstein, Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by grants from Nevus Outreach, Inc., Asociación Española de afectados por Nevus Gigante Congénito, Association du Naevus Géant Congénital, Naevus 2000 France-Europe, Caring Matters Now, the RE(ACT) Community and aid-in-kind from the BeHeard Rare Disease Science Challenge., Université catholique de Lille - Faculté de médecine et de maïeutique (UCL FMM), Université catholique de Lille (UCL), Etchevers, Heather
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Proto-Oncogene Proteins B-raf
0301 basic medicine
Neuroblastoma RAS viral oncogene homolog
Pathology
medicine.medical_specialty
melanocyte
Vascular Malformations
[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Epidermal Cyst
Dermatology
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Biology
General Biochemistry
Genetics and Molecular Biology
BRAF
030207 dermatology & venereal diseases
03 medical and health sciences
0302 clinical medicine
Congenital melanocytic nevus
medicine
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Humans
Nevus
HRAS
skin and connective tissue diseases
neoplasms
Aged
Nevus
Pigmented
venous
GNA11
integumentary system
Vascular malformation
congenital
[SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology
medicine.disease
malformation
030104 developmental biology
Oncology
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Mutation
Venous malformation
GNAQ
[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
nevus
Zdroj: Pigment Cell and Melanoma Research
Pigment Cell and Melanoma Research, In press, ⟨10.1111/pcmr.12685⟩
ISSN: 1755-1471
Popis: International audience; Giant congenital melanocytic nevi may be symptomatically isolated, or syndromic. Associations with capillary malformations are exceptional, and development of epidermal cysts has not been described. A 71-year old patient with a giant congenital melanocytic nevus of the lower back, buttocks and thighs was asymptomatic except for unexpected hemorrhage during partial surgical excision years before. Blunt trauma at age 64 initiated recurrent, severe pain under the nevus; multiple large epidermal cysts developed within it. Imaging and biopsy showed a large, non-pulsatile venous malformation intermingled with the deep nevus. A low-abundance, heterozygous BRAF c.1799T>A (p.V600E) mutation was present in both the gluteal and occipital “satellite” nevi; additional mutations in NRAS, GNAQ, GNA11, HRAS and PIK3CA were undetectable. This is the first demonstration of an identical BRAF mutation in multiple congenital nevi from the same individual, confirming genetic heterogeneity in giant nevi. This exceptional case indicates that constitutive activation of BRAF can be an underlying cause of unusual associations of giant nevi with vascular malformations, and that the latter may be included among the somatic RASopathies.
Databáze: OpenAIRE
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