title: Copy number variation analysis and methylome profiling of a GNAQ-mutant primary meningeal melanocytic tumor and its liver metastasis.
abstract: Primary meningeal melanocytic tumors have genetic similarities with uveal melanomas, including GNAQ or GNA11 mutations. While BAP1 mutations and loss of chromosome 3 have adverse prognostic meaning in uveal melanoma, genetic alterations associated with metastasis have not been investigated in primary meningeal melanocytic tumors. We describe a 43-year-old female with a GNAQ-mutated, BAP1-wt melanocytic tumor originating in the parietal brain region and liver metastases 4years after initial diagnosis. After repeated surgery and chemotherapy she was treated with the immunomodulatory agent ipilimumab. Tissue from the primary and recurrent intracranial tumor (histologically originally diagnosed as intermediate-grade melanocytoma resp. melanoma) and from the liver metastasis was investigated for genome-wide copy number variations and DNA methylation profile. Complete loss of 10p and 19p, partial loss of 16p and a small deletion on 10q were only present in the liver metastasis and not in the intracranial tumors. The DNA methylation profiles of the intracranial tumors and the liver metastasis resembled those of meningeal melanocytomas. In conclusion, in this report we show that a distant metastasis of a meningeal melanocytic tumor has a similar methylation profile as the primary tumor and suggest that particular copy number variations may be associated with metastatic behavior.
authors.affiliation: Department of Pathology, Canisius Wilhelmina Hospital, P.O. Box 9015, 6500 GS Nijmegen, The Netherlands. Electronic address: h.kusters@cwz.nl.
authors.forename: Heidi V N
authors.initials: HV
authors.lastname: Küsters-Vandevelde
authors.affiliation: Department of Medical Oncology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: Vibeke.Kruse@uzgent.be.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Kruse
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: Tom.VanMaerken@ugent.be.
authors.forename: Tom
authors.initials: T
authors.lastname: Van Maerken
authors.affiliation: Department of Radiation Oncology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: Tom.Boterberg@uzgent.be.
authors.forename: Tom
authors.initials: T
authors.lastname: Boterberg
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, P.O. Box 9100, 6500 HB Nijmegen, The Netherlands. Electronic address: Rolph.Pfundt@radboudumc.nl.
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.affiliation: Department of Pathology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.. Electronic address: David.Creytens@uzgent.be.
authors.forename: David
authors.initials: D
authors.lastname: Creytens
authors.affiliation: Department of Pathology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.. Electronic address: cvdbroec@me.com.
authors.forename: Caroline
authors.initials: C
authors.lastname: Van den Broecke
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, P.O. Box 9100, 6500 HB Nijmegen, The Netherlands. Electronic address: Trudi.Machielsen@radboudumc.nl.
authors.forename: Trudi C
authors.initials: TC
authors.lastname: Machielsen
authors.affiliation: Department of Neuropathology, Heidelberg University Hospital, INF 224, 69120 Heidelberg, Germany. Electronic address: Christian.Koelsche@med.uni-heidelberg.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Koelsche
authors.affiliation: Department of Neuropathology, Heidelberg University Hospital, INF 224, 69120 Heidelberg, Germany. Electronic address: Andreas.vonDeimling@med.uni-heidelberg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9100, 6500 HB Nijmegen, The Netherlands; Department of Pathology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: Benno.Kusters@radboudumc.nl.
authors.forename: Benno
authors.initials: B
authors.lastname: Küsters
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9100, 6500 HB Nijmegen, The Netherlands. Electronic address: Patricia.Groenen@radboudumc.nl.
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
authors.affiliation: Department of Pathology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands; Department of Pathology, Princess Máxima Center for Pediatric Oncology and University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: p.wesseling@vumc.nl.
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9100, 6500 HB Nijmegen, The Netherlands. Electronic address: Willeke.Blokx@radboudumc.nl.
authors.forename: Willeke A M
authors.initials: WA
authors.lastname: Blokx
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D003131:Combined Modality Therapy; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D017809:Fatal Outcome; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009154:Mutation; D025521:Tumor Suppressor Proteins / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics
chemical_list: C400134:BAP1 protein, human; C554061:GNAQ protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: Copy number variations; GNAQ; Ipilimumab; Liver metastasis; Meningeal melanocytic tumor; Meningeal melanoma; Methylation