Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells
| العنوان: | Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells |
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| المؤلفون: | Reichel, Jonathan, Chadburn, Amy, Rubinstein, Paul G., Giulino-Roth, Lisa, Tam, Wayne, Liu, Yifang, Gaiolla, Rafael, Eng, Kenneth, Brody, Joshua, Inghirami, Giorgio, Carlo-Stella, Carmelo, Santoro, Armando, Rahal, Daoud, Totonchy, Jennifer, Elemento, Olivier, Cesarman, Ethel, Roshal, Mikhail |
| المساهمون: | Universidade Estadual Paulista (UNESP) |
| بيانات النشر: | Amer Soc Hematology |
| سنة النشر: | 2015 |
| المجموعة: | Universidade Estadual Paulista São Paulo: Acervo Digital da UNESP / São Paulo State University |
| الوصف: | 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. ; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) |
| نوع الوثيقة: | other/unknown material |
| اللغة: | English |
| ردمك: | 978-0-00-350818-5 0-00-350818-8 |
| تدمد: | 0006-4971 |
| العلاقة: | Blood; Blood. Washington: Amer Soc Hematology, v. 125, n. 7, p. 1061-1072, 2015.; http://hdl.handle.net/11449/128305Test; http://acervodigital.unesp.br/handle/11449/128305Test; http://dx.doi.org/10.1182/blood-2014-11-610436Test; WOS:000350818800007; http://www.bloodjournal.org/content/125/7/1061?sso-checked=trueTest |
| DOI: | 10.1182/blood-2014-11-610436 |
| الإتاحة: | https://doi.org/10.1182/blood-2014-11-610436Test http://acervodigital.unesp.br/handle/11449/128305Test http://hdl.handle.net/11449/128305Test http://www.bloodjournal.org/content/125/7/1061?sso-checked=trueTest |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.AD7B9E22 |
| قاعدة البيانات: | BASE |
Full Text Finder | ردمك: | 9780003508185 0003508188 |
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| تدمد: | 00064971 |
| DOI: | 10.1182/blood-2014-11-610436 |