NF1 Mutations Are Common in Desmoplastic Melanoma

被引：83

作者：

Wiesner, Thomas ^{[1
,2
]}

Kiuru, Maija ^{[1
]}

Scott, Sasinya N. ^{[1
,2
]}

Arcila, Maria ^{[1
]}

Halpern, Allan C. ^{[3
]}

Hollmann, Travis ^{[1
]}

Berger, Michael F. ^{[1
,2
]}

Busam, Klaus J. ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Dermatol Serv, Dept Med, New York, NY 10065 USA

来源：

AMERICAN JOURNAL OF SURGICAL PATHOLOGY | 2015年 / 39卷 / 10期

基金：

美国国家卫生研究院;

关键词：

desmoplastic melanoma; neurofibromin; 1; mutation; next-generation sequencing; LYMPH-NODE BIOPSY; MALIGNANT-MELANOMA; NEUROFIBROMATOSIS TYPE-1; GENE; EXPRESSION; PROTEIN; TUMORS; GERMLINE; FREQUENT; S-100;

D O I：

10.1097/PAS.0000000000000451

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Desmoplastic melanoma (DM) is a rare variant of melanoma with distinct clinical, histopathologic, and immunohistochemical features. Clinically, DM differs from conventional melanoma by a higher propensity for local recurrence and less frequent metastatic spread to regional lymph nodes. In its pure form, DM has a distinct appearance displaying a low density of fusiform melanocytes in a collagen-rich matrix. Whereas a number of mutations have been identified in primary melanoma, including BRAF, NRAS, GNAQ, GNA11, and KIT, and the occurrence of these mutations has been found to correlate to some extent with the histopathologic features, anatomic site, and/or mode of sun exposure, no distinct set of mutations has so far been reported for DM. To study the potential association of neurofibromin (NF1) mutations with DM, we examined 15 desmoplastic and 20 non-DMs by next-generation sequencing. Mutations of the NF1 gene were found in 14 of 15 (93%) DMs and 4 of 20 (20%) non-DMs. The high frequency of NF1 mutations in DMs suggests an important role for NF1 in the biology of this type of melanoma.

引用

页码：1357 / 1362

页数：6

共 40 条

[1] An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[2] MUTATIONS IN THE NEUROFIBROMATOSIS-1 GENE IN SPORADIC MALIGNANT-MELANOMA CELL-LINES [J].

ANDERSEN, LB ;

FOUNTAIN, JW ;

GUTMANN, DH ;

TARLE, SA ;

GLOVER, TW ;

DRACOPOLI, NC ;

HOUSMAN, DE ;

COLLINS, FS .

NATURE GENETICS, 1993, 3 (02) :118-121

[3]

[Anonymous], J VIS EXP

[4] Wide excision without radiation for desmoplastic melanoma [J].

Arora, A ;

Lowe, L ;

Su, L ;

Rees, R ;

Bradford, C ;

Cimmino, VC ;

Chang, AE ;

Johnson, TM ;

Sabel, MS .

CANCER, 2005, 104 (07) :1462-1467

[5] Melanoma genome sequencing reveals frequent PREX2 mutations [J].

Berger, Michael F. ;

Hodis, Eran ;

Heffernan, Timothy P. ;

Deribe, Yonathan Lissanu ;

Lawrence, Michael S. ;

Protopopov, Alexei ;

Ivanova, Elena ;

Watson, Ian R. ;

Nickerson, Elizabeth ;

Ghosh, Papia ;

Zhang, Hailei ;

Zeid, Rhamy ;

Ren, Xiaojia ;

Cibulskis, Kristian ;

Sivachenko, Andrey Y. ;

Wagle, Nikhil ;

Sucker, Antje ;

Sougnez, Carrie ;

Onofrio, Robert ;

Ambrogio, Lauren ;

Auclair, Daniel ;

Fennell, Timothy ;

Carter, Scott L. ;

Drier, Yotam ;

Stojanov, Petar ;

Singer, Meredith A. ;

Voet, Douglas ;

Jing, Rui ;

Saksena, Gordon ;

Barretina, Jordi ;

Ramos, Alex H. ;

Pugh, Trevor J. ;

Stransky, Nicolas ;

Parkin, Melissa ;

Winckler, Wendy ;

Mahan, Scott ;

Ardlie, Kristin ;

Baldwin, Jennifer ;

Wargo, Jennifer ;

Schadendorf, Dirk ;

Meyerson, Matthew ;

Gabriel, Stacey B. ;

Golub, Todd R. ;

Wagner, Stephan N. ;

Lander, Eric S. ;

Getz, Gad ;

Chin, Lynda ;

Garraway, Levi A. .

NATURE, 2012, 485 (7399) :502-506

[6] Germline and somatic NF1 mutations in sporadic and NF1-associated malignant peripheral nerve sheath tumours [J].

Bottillo, Irene ;

Ahiquist, Terje ;

Brekke, Helge ;

Danielsen, Stine A. ;

van den Berg, Eva ;

Mertens, Fredrik ;

Lothe, Ragnhild A. ;

Dallapiccola, Bruno .

JOURNAL OF PATHOLOGY, 2009, 217 (05) :693-701

[7] Cutaneous desmoplastic melanoma [J].

Busam, KJ .

ADVANCES IN ANATOMIC PATHOLOGY, 2005, 12 (02) :92-102

[8] Cutaneous desmop astic melanoma - Reappraisal of morphologic heterogeneity and prognostic factors [J].

Busam, KJ ;

Mujumdar, U ;

Hummer, AJ ;

Nobrega, J ;

Hawkins, WG ;

Coit, DG ;

Brady, MS .

AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2004, 28 (11) :1518-1525

[9] Analysis of microphthalmia transcription factor expression in normal tissues and tumors, and comparison of its expression with S-100 protein, gp100, and tyrosinase in desmoplastic malignant melanoma [J].

Busam, KJ ;

Iversen, K ;

Coplan, KC ;

Jungbluth, AA .

AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2001, 25 (02) :197-204

[10] Desmoplastic melanoma: A review [J].

Chen, Lucy L. ;

Jaimes, Natalia ;

Barker, Christopher A. ;

Busam, Klaus J. ;

Marghoob, Ashfaq A. .

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2013, 68 (05) :825-833

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