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http://acervodigital.unesp.br/handle/11449/128305
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DC Field | Value | Language |
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dc.contributor.author | Reichel, Jonathan | - |
dc.contributor.author | Chadburn, Amy | - |
dc.contributor.author | Rubinstein, Paul G. | - |
dc.contributor.author | Giulino-Roth, Lisa | - |
dc.contributor.author | Tam, Wayne | - |
dc.contributor.author | Liu, Yifang | - |
dc.contributor.author | Gaiolla, Rafael | - |
dc.contributor.author | Eng, Kenneth | - |
dc.contributor.author | Brody, Joshua | - |
dc.contributor.author | Inghirami, Giorgio | - |
dc.contributor.author | Carlo-Stella, Carmelo | - |
dc.contributor.author | Santoro, Armando | - |
dc.contributor.author | Rahal, Daoud | - |
dc.contributor.author | Totonchy, Jennifer | - |
dc.contributor.author | Elemento, Olivier | - |
dc.contributor.author | Cesarman, Ethel | - |
dc.contributor.author | Roshal, Mikhail | - |
dc.date.accessioned | 2015-10-21T13:08:51Z | - |
dc.date.accessioned | 2016-10-25T20:59:17Z | - |
dc.date.available | 2015-10-21T13:08:51Z | - |
dc.date.available | 2016-10-25T20:59:17Z | - |
dc.date.issued | 2015-02-12 | - |
dc.identifier | http://www.bloodjournal.org/content/125/7/1061?sso-checked=true | - |
dc.identifier.citation | Blood. Washington: Amer Soc Hematology, v. 125, n. 7, p. 1061-1072, 2015. | - |
dc.identifier.issn | 0006-4971 | - |
dc.identifier.uri | http://hdl.handle.net/11449/128305 | - |
dc.identifier.uri | http://acervodigital.unesp.br/handle/11449/128305 | - |
dc.description.abstract | Classical Hodgkin lymphoma (cHL) is characterized by sparsely distributed Hodgkin and Reed-Sternberg (HRS) cells amid reactive host background, complicating the acquisition of neoplastic DNA without extensive background contamination. We overcame this limitation by using flow-sorted HRS and intratumor T cells and optimized low-input exome sequencing of 10 patient samples to reveal alterations in genes involved in antigen presentation, chromosome integrity, transcriptional regulation, and ubiquitination. beta-2-microglobulin (B2M) is the most commonly altered gene in HRS cells, with 7 of 10 cases having inactivating mutations that lead to loss of major histocompatibility complex class I (MHC-I) expression. Enforced wild-type B2M expression in a cHL cell line restored MHC-I expression. In an extended cohort of 145 patients, the absence of B2M protein in the HRS cells was associated with lower stage of disease, younger age at diagnosis, and better overall and progression-free survival. B2M-deficient cases encompassed most of the nodular sclerosis subtype cases and only a minority of mixed cellularity cases, suggesting that B2M deficiency determines the tumor microenvironment and may define a major subset of cHL that has more uniform clinical and morphologic features. In addition, we report previously unknown genetic alterations that may render selected patients sensitive to specific targeted therapies. | en |
dc.description.sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) | - |
dc.format.extent | 1061-1072 | - |
dc.language.iso | eng | - |
dc.publisher | Amer Soc Hematology | - |
dc.source | Web of Science | - |
dc.title | Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells | en |
dc.type | outro | - |
dc.contributor.institution | Weill Cornell Medical College | - |
dc.contributor.institution | Tri-Institutional Training Program in Computational Biology and Medicine | - |
dc.contributor.institution | Northwestern University | - |
dc.contributor.institution | Rush University Medical Center | - |
dc.contributor.institution | Universidade Estadual Paulista (UNESP) | - |
dc.contributor.institution | Icahn School of Medicine at Mount Sinai | - |
dc.contributor.institution | Humanitas Clinical and Research Center | - |
dc.contributor.institution | University of Milan | - |
dc.description.affiliation | Weill Cornell Medical College, Department of Pathology and Laboratory Medicine | - |
dc.description.affiliation | Northwestern University, Department of Pathology, Feinberg School of Medicine | - |
dc.description.affiliation | Rush University Medical Center, John H. Stroger Jr Hospital of Cook County | - |
dc.description.affiliation | Weill Cornell Medical College, Department of Pediatrics | - |
dc.description.affiliation | Humanitas Clinical and Research Center, Humanitas Cancer Center | - |
dc.description.affiliation | University of Milan, School of Medicine | - |
dc.description.affiliation | Weill Cornell Medical College, Institute for Computational Biomedicine | - |
dc.description.affiliationUnesp | Universidade Estadual Paulista, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu | - |
dc.identifier.doi | http://dx.doi.org/10.1182/blood-2014-11-610436 | - |
dc.identifier.wos | WOS:000350818800007 | - |
dc.rights.accessRights | Acesso restrito | - |
dc.relation.ispartof | Blood | - |
Appears in Collections: | Artigos, TCCs, Teses e Dissertações da Unesp |
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