MYC high level gene amplification is a distinctive feature of angiosarcomas after irradiation or chronic lymphedema
Johanna Manner,Bernhard Radlwimmer,Peter Hohenberger,Katharina Mössinger,Stefan Küffer,Christian Sauer,Djeda Belharazem,Andreas Zettl,Jean-Michel Coindre,Christian Hallermann,Jörg T. Hartmann,Detlef Katenkamp,Kathrin Katenkamp,Patrick Schöffski,Raphael Sciot,Agnieszka Wozniak,Peter Lichter,Alexander Marx,Philipp Ströbel +18 more
Reads0
Chats0
TLDR
Secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of MYC, which may have implications both for the diagnosis and treatment of these tumors.Abstract:
Angiosarcomas (AS) are rare vascular malignancies that arise either de novo as primary tumors or secondary to irradiation or chronic lymphedema. The cytogenetics of angiosarcomas are poorly characterized. We applied array-comparative genomic hybridization as a screening method to identify recurrent alterations in 22 cases. Recurrent genetic alterations were identified only in secondary but not in primary AS. The most frequent recurrent alterations were high level amplifications on chromosome 8q24.21 (50%), followed by 10p12.33 (33%) and 5q35.3 (11%). Fluorescence in situ hybridization analysis in 28 primary and 33 secondary angiosarcomas (31 tumors secondary to irradiation, 2 tumors secondary to chronic lymphedema) confirmed high level amplification of MYC on chromosome 8q24.21 as a recurrent genetic alteration found exclusively in 55% of AS secondary to irradiation or chronic lymphedema, but not in primary AS. Amplification of MYC did not predispose to high grade morphology or increased cell turnover. In conclusion, despite their identical morphology, secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of MYC. This finding may have implications both for the diagnosis and treatment of these tumors.read more
Citations
More filters
Journal ArticleDOI
The evolving classification of soft tissue tumours – an update based on the new 2013 WHO classification
TL;DR: A brief overview summarizes changes in the classification in each of the broad categories of soft tissue tumour (adipocytic, fibroblastic, etc.) and also provides a short summary of newer genetic data which have been incorporated in the WHO classification.
Journal ArticleDOI
WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition.
TL;DR: The fourth edition of the World Health Organization (WHO) Classification of Tumours of Soft Tissue and Bone was published in February 2013, and serves to provide an updated classification scheme and reproducible diagnostic criteria for pathologists.
Journal ArticleDOI
The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes
Alexander Marx,John K.C. Chan,Jean-Michel Coindre,Frank C. Detterbeck,Nicolas Girard,Nancy L. Harris,Elaine S. Jaffe,Michael O. Kurrer,Edith M. Marom,Andre L. Moreira,Kiyoshi Mukai,Attilio Orazi,Philipp Ströbel +12 more
TL;DR: The 4th edition of the World Health Organization (WHO) Classification of thymic tumors has two aims: 1) to comprehensively list the established and new tumor entities and variants that are described in the new WHO Classification of Thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and mediastinum; and 2) to highlight major differences in this classification that result from the progress that has been made since the 3rd edition in 2004 at
Journal ArticleDOI
Refinements in Sarcoma Classification in the Current 2013 World Health Organization Classification of Tumours of Soft Tissue and Bone
Vickie Y. Jo,Leona A. Doyle +1 more
TL;DR: The fourth edition of the World Health Organization (WHO) Classification of Tumours of Soft Tissue and Bone was published in February 2013 and provides an updated classification scheme and reproducible diagnostic criteria, based on recent clinicopathologic studies and genetic and molecular data.
Journal ArticleDOI
Consistent MYC and FLT4 Gene Amplification in Radiation-Induced Angiosarcoma but not in other Radiation-Associated Atypical Vascular Lesions
TL;DR: The findings reinforce the distinct pathogenesis of AS subtypes, with MYC amplification being an early, but necessary event in secondary AS, and gene‐expression profiling distinguishes two AS genomic clusters, which correlate with anatomical location and prior exposure to radiation.
References
More filters
Journal ArticleDOI
Soft Tissue Tumors
TL;DR: The comprehensive nature of the work includes not only soft-tissue tumors, in the traditional sense, but also provides extensive analyses of lesions that are peripheral to the tumor designation, most strikingly in the sections on fibrous proliferations and fibromatoses.
Journal ArticleDOI
Cardiovascular Failure in Mouse Embryos Deficient in VEGF Receptor-3
Daniel J. Dumont,Lotta Jussila,Jussi Taipale,Athina Lymboussaki,Tuija Mustonen,Katri Pajusola,Martin L. Breitman,Kari Alitalo +7 more
TL;DR: It is shown that targeted inactivation of the gene encoding VEGFR-3 resulted in defective blood vessel development in early mouse embryos, indicating an essential role in the development of the embryonic cardiovascular system before the emergence of the lymphatic vessels.
Journal ArticleDOI
Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation
Tuomas Tammela,Georgia Zarkada,Elisabet Wallgard,Aino Murtomäki,Steven Suchting,Maria Wirzenius,Marika Waltari,Mats Hellström,Tibor Schomber,Reetta Peltonen,Catarina Freitas,Antonio Duarte,Helena Isoniemi,Pirjo Laakkonen,Gerhard Christofori,Seppo Ylä-Herttuala,Masabumi Shibuya,Bronislaw Pytowski,Anne Eichmann,Christer Betsholtz,Kari Alitalo +20 more
TL;DR: It is demonstrated that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting or blocking of VEG FR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models, implicate VEGfr-3 as a regulator of vascular network formation.
Journal ArticleDOI
Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma
Louis Guillou,J.-M. Coindre,Françoise Bonichon,B. Bui Nguyen,P. Terrier,F. Collin,Marie-Odile Vilain,A. M. Mandard,V Le Doussal,A. Leroux,Jocelyne Jacquemier,H Duplay,Xavier Sastre-Garau,J Costa +13 more
TL;DR: The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality, and the use of this system to evaluate STS aggressiveness might be favored.
Journal ArticleDOI
Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC
Meenakshi Jain,Constadina Arvanitis,Kenneth Chu,William C. Dewey,Edith A. Leonhardt,Maxine Trinh,Christopher D. Sundberg,J. Michael Bishop,Dean W. Felsher +8 more
TL;DR: It is demonstrated that brief inactivation of MYC results in the sustained regression of tumors and the differentiation of osteogenic sarcoma cells into mature osteocytes, raising the possibility that transient in activation ofMYC may be an effective therapy for certain cancers.
Related Papers (5)
Recurrent PTPRB and PLCG1 mutations in angiosarcoma
Sam Behjati,Sam Behjati,Patrick S. Tarpey,Helen Sheldon,Inigo Martincorena,Peter Van Loo,Peter Van Loo,Gunes Gundem,David C. Wedge,Manasa Ramakrishna,Susanna L. Cooke,Nischalan Pillay,Nischalan Pillay,Hans Kristian Moen Vollan,Hans Kristian Moen Vollan,Hans Kristian Moen Vollan,Elli Papaemmanuil,Hans Koss,Hans Koss,Tom D. Bunney,Claire Hardy,Olivia Joseph,Sancha Martin,Laura Mudie,Adam Butler,Jon W. Teague,M Patil,Graham Steers,Yu Cao,Curtis Gumbs,Davis R. Ingram,Alexander J. Lazar,Latasha Little,Harshad S. Mahadeshwar,Alexei Protopopov,Ghadah A. Al Sannaa,Sahil Seth,Xingzhi Song,Jiabin Tang,Jianhua Zhang,Vinod Ravi,Keila E. Torres,Bhavisha Khatri,Dina Halai,Ioannis Roxanis,Daniel Baumhoer,Roberto Tirabosco,M Fernanda Amary,Chris Boshoff,Chris Boshoff,Ultan McDermott,Matilda Katan,Michael R. Stratton,P. Andrew Futreal,Adrienne M. Flanagan,Adrienne M. Flanagan,Adrian L. Harris,Adrian L. Harris,Peter J. Campbell,Peter J. Campbell +59 more