Melanotic Tumors of the Nervous System are Characterized by Distinct Mutational, Chromosomal and Epigenomic Profiles

被引：58

作者：

Koelsche, Christian ^{[1
,5
]}

Hovestadt, Volker ^{[6
]}

Jones, David T. W. ^{[7
]}

Capper, David ^{[1
,5
]}

Sturm, Dominik ^{[2
,7
]}

Sahm, Felix ^{[1
,5
]}

Schrimpf, Daniel ^{[1
]}

Adeberg, Sebastian ^{[3
]}

Boehmer, Katja ^{[1
]}

Hagenlocher, Christian ^{[5
]}

Mechtersheimer, Gunhild ^{[4
]}

Kohlhof, Patricia ^{[9
]}

Muehleisen, Helmut ^{[10
]}

Beschorner, Rudi ^{[11
]}

Hartmann, Christian ^{[12
]}

Braczynski, Anne Kristin ^{[13
]}

Mittelbronn, Michel ^{[8
,13
]}

Buslei, Rolf ^{[14
]}

Becker, Albert ^{[15
]}

Grote, Alexander ^{[16
]}

Urbach, Horst ^{[17
]}

Staszewski, Ori ^{[18
]}

Prinz, Marco ^{[19
]}

Hewer, Ekkehard ^{[20
]}

Pfister, Stefan M. ^{[2
,7
]}

von Deimling, Andreas ^{[1
,5
]}

Reuss, David E. ^{[1
,5
]}

机构：

[1] Univ Med Ctr, Inst Pathol, Dept Neuropathol, Heidelberg, Germany

[2] Univ Med Ctr, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany

[3] Univ Med Ctr, Dept Radiat Oncol, Heidelberg, Germany

[4] Univ Med Ctr, Inst Pathol, Dept Gen Pathol, Heidelberg, Germany

[5] German Canc Consortium DKTK, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[6] German Canc Consortium DKTK, Div Mol Genet, Heidelberg, Germany

[7] German Canc Consortium DKTK, Div Pediat Neurooncol, Heidelberg, Germany

[8] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[9] Stuttgart Hosp, Inst Pathol, Stuttgart, Germany

[10] Ludwigsburg Hosp, Inst Pathol & Neuropathol, Ludwigsburg, Germany

[11] Univ Hosp, Dept Neuropathol, Tubingen, Germany

[12] Hannover Med Sch, Dept Neuropathol, Hannover, Germany

[13] Goethe Univ Frankfurt, Neurol Inst, Edinger Inst, D-60054 Frankfurt, Germany

[14] Univ Erlangen Nurnberg, Dept Neuropathol, D-91054 Erlangen, Germany

[15] Univ Med Ctr, Inst Neuropathol, Bonn, Germany

[16] Univ Med Ctr, Dept Neurosurg, Bonn, Germany

[17] Univ Med Ctr, Dept Neuroradiol, Freiburg, Germany

[18] Univ Med Ctr, Inst Neuropathol, Freiburg, Germany

[19] Univ Freiburg, BIOSS Ctr Biol Signaling Studies, D-79106 Freiburg, Germany

[20] Univ Bern, Dept Pathol, CH-3000 Bern, Switzerland

来源：

BRAIN PATHOLOGY | 2015年 / 25卷 / 02期

关键词：

450k; copy number variants; GNA11; GNAQ; melanocytoma; melanoma; melanotic schwannoma; TERT promoter; TERT PROMOTER MUTATIONS; PRIMARY MELANOCYTIC NEOPLASMS; UVEAL MELANOMA; MENINGEAL MELANOCYTOMA; GNAQ; SCHWANNOMA; LESIONS; RAS;

D O I：

10.1111/bpa.12228

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Melanotic tumors of the nervous system show overlapping histological characteristics but differ substantially in their biological behavior. In order to achieve a better delineation of such tumors, we performed an in-depth molecular characterization. Eighteen melanocytomas, 12 melanomas, and 14 melanotic and 14 conventional schwannomas (control group) were investigated for methylome patterns (450k array), gene mutations associated with melanotic tumors and copy number variants (CNVs). The methylome fingerprints assigned tumors to entity-specific groups. Methylation groups also showed a substantial overlap with histology-based diagnosis suggesting that they represent true biological entities. On the molecular level, melanotic schwannomas were characterized by a complex karyotype with recurrent monosomy of chromosome 22q and variable whole chromosomal gains and recurrent losses commonly involving chromosomes 1, 17p and 21. Melanocytomas carried GNAQ/11 mutations and presented with CNV involving chromosomes 3 and 6. Melanomas were frequently mutated in the TERT promoter, harbored additional oncogene mutations and showed recurrent chromosomal losses involving chromosomes 9, 10 and 6q, as well as gains of 22q. Together, melanotic nervous system tumors have several distinct mutational and chromosomal alterations and can reliably be distinguished by methylome profiling.

引用

页码：202 / 208

页数：7

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