Activating mutations in the MAP-kinase pathway define non-ossifying fibroma of bone

被引：48

作者：

Baumhoer, Daniel ^{[1
,2
]}

Kovac, Michal ^{[1
,2
]}

Sperveslage, Jan ^{[3
]}

Ameline, Baptiste ^{[1
,2
]}

Strobl, Anna-Christina ^{[4
]}

Krause, Arthur ^{[1
,2
]}

Trautmann, Marcel ^{[3
,5
]}

Wardelmann, Eva ^{[3
]}

Nathrath, Michaela ^{[6
,7
,8
]}

Hoeller, Sylvia ^{[1
,2
]}

Hardes, Jendrik ^{[9
,10
]}

Gosheger, Georg ^{[9
]}

Krieg, Andreas H. ^{[11
]}

Vieth, Volker ^{[12
]}

Tirabosco, Roberto ^{[4
]}

Amary, Fernanda ^{[4
]}

Flanagan, Adrienne M. ^{[4
,13
]}

Hartmann, Wolfgang ^{[3
,5
]}

机构：

[1] Univ Hosp Basel, Inst Pathol, Bone Tumour Reference Ctr, Basel, Switzerland

[2] Univ Basel, Basel, Switzerland

[3] Univ Hosp Munster, Gerhard Domagk Inst Pathol, Munster, Germany

[4] Royal Natl Orthopaed Hosp NHS Trust, Histopathol Dept, Stanmore, Middx, England

[5] Univ Hosp Munster, Gerhard Domagk Inst Pathol, Div Translat Pathol, Munster, Germany

[6] Klinikum Kassel, Dept Pediat Oncol, Kassel, Germany

[7] Tech Univ Munich, Klinikum Rech Isar, Chikkens Canc Res Ctr, Munich, Germany

[8] Tech Univ Munich, Klinikum Rech Isar, Dept Pediat, Munich, Germany

[9] Univ Hosp Munster, Dept Orthopaed & Tumour Orthopaed, Munster, Germany

[10] Westdeutsch Tumorzentrum, Sarcoma Ctr Essen, Dept Musculoskeletal Surg, Essen, Germany

[11] Univ Childrens Hosp Basel, Paediat Orthopaed Dept, Basel, Switzerland

[12] Klinikum Ibbenburen, Dept Radiol, Ibbenburen, Germany

[13] UCL Canc Inst, Dept Pathol, London, England

来源：

JOURNAL OF PATHOLOGY | 2019年 / 248卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

Non-ossifying fibroma; bone tumour; KRAS; FGFR1; NF1; massively parallel sequencing; BRAF MUTATIONS; FGFR3; MUTATIONS; DYSPLASIA; SPECTRUM; CELLS; AGE;

D O I：

10.1002/path.5216

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Non-ossifying fibroma (NOF), which occasionally results in pathologic fracture, is considered the most common benign and self-limiting lesion of the growing skeleton. By DNA sequencing we have identified hotspot KRAS, FGFR1 and NF1 mutations in 48 of 59 patients (81.4%) with NOF, at allele frequencies ranging from 0.04 to 0.61. Our findings define NOF as a genetically driven neoplasm caused in most cases by activated MAP-kinase signalling. Interestingly, this driving force either diminishes over time or at least is not sufficient to prevent autonomous regression and resolution. Beyond its contribution to a better understanding of the molecular pathogenesis of NOF, this study adds another benign lesion to the spectrum of KRAS- and MAP-kinase signalling-driven tumours. Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

引用

页码：116 / 122

页数：7

共 27 条

[1] Cancer-Associated Mutations in Endometriosis without Cancer [J].

Anglesio, M. S. ;

Papadopoulos, N. ;

Ayhan, A. ;

Nazeran, T. M. ;

Noe, M. ;

Horlings, H. M. ;

Lum, A. ;

Jones, S. ;

Senz, J. ;

Seckin, T. ;

Ho, J. ;

Wu, R. -C. ;

Lac, V. ;

Ogawa, H. ;

Tessier-Cloutier, B. ;

Alhassan, R. ;

Wang, A. ;

Wang, Y. ;

Cohen, J. D. ;

Wong, F. ;

Hasanovic, A. ;

Orr, N. ;

Zhang, M. ;

Popoli, M. ;

McMahon, W. ;

Wood, L. D. ;

Mattox, A. ;

Allaire, C. ;

Segars, J. ;

Williams, C. ;

Tomasetti, C. ;

Boyd, N. ;

Kinzler, K. W. ;

Gilks, C. B. ;

Diaz, L. ;

Wang, T. -L. ;

Vogelstein, B. ;

Yong, P. J. ;

Huntsman, D. G. ;

Shih, I. -M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (19) :1835-1848

[2] Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution [J].

Baker, Ann-Marie ;

Huang, Weini ;

Wang, Xiao-Ming Mindy ;

Jansen, Marnix ;

Ma, Xiao-Jun ;

Kim, Jeffrey ;

Anderson, Courtney M. ;

Wu, Xingyong ;

Pan, Liuliu ;

Su, Nan ;

Luo, Yuling ;

Domingo, Enric ;

Heide, Timon ;

Sottoriva, Andrea ;

Lewis, Annabelle ;

Beggs, Andrew D. ;

Wright, Nicholas A. ;

Rodriguez-Justo, Manuel ;

Park, Emily ;

Tomlinson, Ian ;

Graham, Trevor A. .

NATURE COMMUNICATIONS, 2017, 8

[3] Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis [J].

Bennett, James T. ;

Tan, Tiong Yang ;

Alcantara, Diana ;

Tetrault, Martine ;

Timms, Andrew E. ;

Jensen, Dana ;

Collins, Sarah ;

Nowaczyk, Malgorzata J. M. ;

Lindhurst, Marjorie J. ;

Christensen, Katherine M. ;

Braddock, Stephen R. ;

Brandling-Bennett, Heather ;

Hennekam, Raoul C. M. ;

Chung, Brian ;

Lehman, Anna ;

Su, John ;

Ng, SuYuen ;

Amor, David J. ;

Majewski, Jacek ;

Biesecker, Les G. ;

Boycott, Kym M. ;

Dobyns, William B. ;

O'Driscoll, Mark ;

Moog, Ute ;

McDonell, Laura M. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2016, 98 (03) :579-587

[4] KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment [J].

Carvalho, Patricia Dias ;

Guimaraes, Carlos F. ;

Cardoso, Ana P. ;

Mendonca, Susana ;

Costa, Angela M. ;

Oliveira, Maria J. ;

Velho, Sergia .

CANCER RESEARCH, 2018, 78 (01) :7-14

[5] FGFR3 mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization [J].

Hafner, Christian ;

Hartmann, Arndt ;

van Oers, Johanna M. M. ;

Stoehr, Robert ;

Zwarthoff, Ellen C. ;

Hofstaedter, Ferdinand ;

Landthaler, Michael ;

Vogt, Thomas .

MODERN PATHOLOGY, 2007, 20 (08) :895-903

[6] Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi [J].

Hafner, Christian ;

van Oers, Johanna M. M. ;

Vogt, Thomas ;

Landthaler, Michael ;

Stoehr, Robert ;

Blaszyk, Hagen ;

Hofstaedter, Ferdinand ;

Zwarthoff, Ellen C. ;

Hartmann, Arndt .

JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (08) :2201-2207

[7] Multiple oncogenic mutations and clonal relationship in spatially distinct benign human epidermal tumors [J].

Hafner, Christian ;

Toll, Agusti ;

Fernandez-Casado, Alejandro ;

Earl, Julie ;

Marques, Miriam ;

Acquadro, Francesco ;

Mendez-Pertuz, Marinela ;

Urioste, Miguel ;

Malats, Nuria ;

Burns, Julie E. ;

Knowles, Margaret A. ;

Cigudosa, Juan C. ;

Hartmann, Arndt ;

Vogt, Thomas ;

Landthaler, Michael ;

Pujol, Ramon M. ;

Real, Francisco X. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (48) :20780-20785

[8] The Conundrum of Genetic "Drivers" in Benign Conditions [J].

Kato, Shumei ;

Lippman, Scott M. ;

Flaherty, Keith T. ;

Kurzrock, Razelle .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2016, 108 (08)

[9] BRAF mutations are common somatic events in melanocytic nevi [J].

Kumar, R ;

Angelini, S ;

Snellman, E ;

Hemminki, K .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2004, 122 (02) :342-348

[10] Age-Dependent Demise of GNAS-Mutated Skeletal Stem Cells and "Normalization" of Fibrous Dysplasia of Bone [J].

Kuznetsov, Sergei A. ;

Cherman, Natasha ;

Riminucci, Mara ;

Collins, Michael T. ;

Robey, Pamela Gehron ;

Bianco, Paolo .

JOURNAL OF BONE AND MINERAL RESEARCH, 2008, 23 (11) :1731-1740

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