STAT6 is amplified in a subset of dedifferentiated liposarcoma

Modern Pathology

Volumn 27, Issue 9, 2014, Pages 1231-1237

  Doyle, Leona A ^a   Tao, Derrick ^a   Mariño Enríquez, Adrián ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Amplification; Dedifferentiated liposarcoma; Sarcoma; Solitary fibrous tumor; STAT6

Indexed keywords

CYCLIN DEPENDENT KINASE 4; PROTEIN MDM2; STAT6 PROTEIN; STAT6 PROTEIN, HUMAN; TUMOR MARKER;

ADULT; AGED; ARTICLE; CANCER CHEMOTHERAPY; CANCER PATIENT; CANCER RADIOTHERAPY; CANCER SURGERY; CASE REPORT; COMPARATIVE STUDY; CONTROLLED STUDY; CYTOGENETICS; DEDIFFERENTIATED LIPOSARCOMA; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; GENE AMPLIFICATION; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MALE; MARKER CHROMOSOME; PRIORITY JOURNAL; PROTEIN DEGRADATION; SOLITARY FIBROUS TUMOR; TISSUE SECTION; GENETICS; KIDNEY TUMOR; LIPOSARCOMA; MEDIASTINUM TUMOR; METABOLISM; MIDDLE AGED; TESTIS TUMOR;

AGED; CYCLIN-DEPENDENT KINASE 4; FEMALE; GENE AMPLIFICATION; HUMANS; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION, FLUORESCENCE; KIDNEY NEOPLASMS; LIPOSARCOMA; MALE; MEDIASTINAL NEOPLASMS; MIDDLE AGED; PROTO-ONCOGENE PROTEINS C-MDM2; STAT6 TRANSCRIPTION FACTOR; TESTICULAR NEOPLASMS; TUMOR MARKERS, BIOLOGICAL;

EID: 84925228865     PISSN: 08933952     EISSN: 15300285     Source Type: Journal    
DOI: 10.1038/modpathol.2013.247     Document Type: Article

References (25)

1. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds). WHO Classification of Tumours of Soft Tissue and Bone. 4th edn. IARC: Lyon, France; 2013, pp 468.
2. McCormick D, Mentzel T, Beham A, et al. Dedifferentiated liposarcoma. Clinicopathologic analysis of 32 cases suggesting a better prognostic subgroup among pleomorphic sarcomas. Am J Surg Pathol 1994;18:1213-1223.
3. Crago AM, Singer S. Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma. Curr Opin Oncol 2011;23:373-378.
4. Garsed DW, Holloway AJ, Thomas DM. Cancer-associated neochromosomes: a novel mechanism of oncogenesis. Bioessays 2009;31:1191-1200.
5. Pedeutour F, Forus A, Coindre JM, et al. Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer 1999;24:30-41.
6. Italiano A, Bianchini L, Keslair F, et al. HMGA2 is the partner of MDM2 in well-differentiated and dedifferentiated liposarcomas whereas CDK4 belongs to a distinct inconsistent amplicon. Int J Cancer 2008;122:2233-2241.
7. Persson F, Olofsson A, Sjogren H, et al. Characterization of the 12q amplicons by high-resolution, oligonucleotide array CGH and expression analyses of a novel liposarcoma cell line. Cancer Lett 2008;260:37-47.
8. Snyder EL, Sandstrom DJ, Law K, et al. C-jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme. J Pathol 2009;218:292-300.
9. Ray-Coquard I, Blay JY, Italiano A, et al. Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Lancet Oncol 2012;13:1133-1140.
10. Pedeutour F, Suijkerbuijk RF, Forus A, et al. Complex composition and co-amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcoma. Genes Chromosomes Cancer 1994;10:85-94.
11. Dei Tos AP, Doglioni C, Piccinin S, et al. Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours. J Pathol 2000;190:531-536.
12. Wang X, Asmann YW, Erickson-Johnson MR, et al. High-resolution genomic mapping reveals consistent amplification of the fibroblast growth factor receptor substrate 2 gene in well-differentiated and dedifferentiated liposarcoma. Genes Chromosomes Cancer 2011;50:849-858.
13. Italiano A, Bianchini L, Gjernes E, et al. Clinical and biological significance of CDK4 amplification in well-differentiated and dedifferentiated liposarcomas. Clin Cancer Res 2009;15:5696-5703.
14. Barretina J, Taylor BS, Banerji S, et al. Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet 2010;42:715-721.
15. Binh MB, Sastre-Garau X, Guillou L, et al. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surg Pathol 2005;29:1340-1347.
16. Conyers R, Young S, Thomas DM. Liposarcoma: molecular genetics and therapeutics. Sarcoma 2011;2011:483154.
17. Buettner R, Mora LB, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 2002;8:945-954.
18. Robinson DR, Wu YM, Kalyana-Sundaram S, et al. Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet 2013;45:180-185.
19. Mohajeri A, Tayebwa J, Collin A, et al. Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor. Genes Chromosomes Cancer 2013;52:873-886.
20. Doyle LA, Vivero M, Fletcher CD, et al. Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol advance online publication, 13 September 2013; doi:10.1038/modpathol.2013.164 (e-pub ahead of print).
21. Schweizer L, Koelsche C, Sahm F, et al. Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein. Acta Neuropathol 2013;125:651-658.
22. Lee JC, Fletcher CD. Malignant fat-forming solitary fibrous tumor (so-called 'lipomatous hemangiopericytoma'): clinicopathologic analysis of 14 cases. Am J Surg Pathol 2011;35:1177-1185.
23. Guillou L, Gebhard S, Coindre JM. Lipomatous hemangiopericytoma: a fat-containing variant of solitary fibrous tumor? Clinicopathologic, immunohistochemical, and ultrastructural analysis of a series in favor of a unifying concept. Hum Pathol 2000;31:1108-1115.
24. Nilbert M, Rydholm A, Mitelman F, et al. Characterization of the 12q13-15 amplicon in soft tissue tumors. Cancer Genet Cytogenet 1995;83:32-36.
25. Gisselsson D, Pettersson L, Hoglund M, et al. Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity. Proc Natl Acad Sci U S A 2000;97:5357-5362.