Status in Diffuse Large B Cell Lymphoma not otherwise specified: A single center study from Argentina

BackgroundDiffuse large B-cell Lymphoma (DLBCL) is a heterogeneous disease. Based on Hans? algorithm, DLBCL not otherwise specified (NOS) is classified by cell-of-origin into germinal center B-cell (GCB) and non-GCB subtypes. Non-GCB ones have frequently NF-kB pathway activation and worse prognosis compared to GCB cases. MYD88 is an adaptor protein of toll-like and IL-1 receptor signalling, leading downstream NF-kB pathway activation. MYD88 L265P mutation confers the protein constitutional activation. This mutation is present in around 20% of non-GCB subtype, and rarely found in GCB subtype of DLBCL. The prognostic value of MYD88 L265P mutation in DLBCL has been matter of controversy.AimsThe aim of the study was to determine the prevalence of MYD88 L265P mutation in DLBCL NOS cases of Argentina, and compare it with previous reports in the literature.MethodsA retrospective cohort of 73 DLBCL NOS cases diagnosed in the Italian Hospital of Buenos Aires (Argentina) between 2010 and 2016 was studied. Complete clinical records, Hans? algorithm, and available material for molecular testing were inclusion criteria. Patients with prior diagnosis of low-grade lymphoma or diagnosis of immunodeficiency-associated, post-transplant, EBV+, primary mediastinal, primary testicular, primary CNS, primary effusion, leg-type or intravascular DLBCL were excluded. DNA was extracted from tissue blocks using QIAamp mini kit (Qiagen). MYD88 L265P was assessed using an in-house allele-specific probe-based Real-Time PCR assay. Positive (primary testicular DLBCL) and negative controls (tonsil) were added to each run. Every case was checked subsequently using qBiomarker MYD88 L265P Somatic Mutation Assay (Qiagen). Prevalences were expressed as percentage, confident intervals were calculated using Clopper-Pearson exact method. Kaplan Meier curves and Log-rank test were used to evaluate overall survival (OS).Results36 patients (49,31%) were female, and median age at diagnosis was 66 years (range 26-89). 33 patients (45,20%) had extranodal involvement (gastrointestinal tract: 14 cases; liver: 5 cases; bone: 4 cases; other locations: 10 cases). 44 cases (60,27%) were GCB and 29 (39,73%) were non-GCB DLBCLs. MYD88 L265P mutation was present in 2 cases (2,74% ; CI 95%: 0,33-9,55%) among all DLBCLs, including 1 GCB case (2,27% ; CI 95%: 0,06-12,02%) and 1 non-GCB case (3,45% ; CI 95%: 0,09-17.76%). There was no significant association between MYD88 L265P status, Hans´algorithm subtype, sex, age or Ki67 index and OS.ConclusionIn the analyzed population, the prevalence of GCB and non-GCB subtypes among DLBCL NOS cases was similar to international reports, although we did not find significant difference between both groups regarding OS (p=0,712). MYD88 L265P mutation was found only in 2 patients (1 GCB and 1 non-GCB), accounting for 2,74% (CI 95%: 0,33-9,55%) and 2,27% (CI 95%: 0,06-12,02%) of all DLBCL NOS and non-GCB cases, respectively. Both prevalences are significantly lower than those published in 2017 by Lee et al. in a meta-analysis, where they found that MYD88 L265P is present in 16% (CI 95%: 15-18,09%) and 20,63% (CI 95%: 18,41-23%) of patients among all DLBCLs and non-GCB subtype, respectively. However, MYD88 L265P prevalence in primary SNC, testicular and leg-type DLBCLs diagnosed in our institution are similar to the literature (data not shown).Fil: Jauk, Federico. Hospital Italiano; ArgentinaFil: Kohan, Dana. Hospital Italiano; ArgentinaFil: Ortega, Leandro Ismael. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diaz de Arce, Heidy. Hospital Italiano; ArgentinaFil: Cristaldo, Nancy. Hospital Italiano; ArgentinaFil: RANUNCOLO, Stella Maris. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Warley, Fernando. Hospital Italiano; ArgentinaFil: Otero, Victoria. Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan Jorge. Hospital Italiano; Argentina24th Congress of the European Hematology AssociationAmsterdamHolandaEscuela Europea de Hematologí

Plasma metalloproteinase activity is enhanced in the euglobulin fraction of breast and lung cancer patients

Matrix metalloproteinases (MMP) have been implicated in tumor invasion and metastasis. We verified, by gelatin zymography, MMP activity in the euglobulin plasma fraction of 82 healthy controls, 66 patients with benign diseases and 149 patients with breast, lung, colon or brain cancer. The euglobulin fractions assayed showed 4 gelatinolytic bands of 62, 92, 120 and 200 kDa. The median (Md) value for 92 kDa-MMP activity was significantly increased in breast (Md 1.34 arbitrary units [AU]/ml plasma, range 0.0–7.2) and lung cancer patients (Md 1.43 AU/ml, range 0.0–3.6) compared with the controls (Md 0.48 AU/ml, range 0.0–1.8). Patients with colon cancer or gliomas presented values of MMP-9 similar to those of the healthy population. Multivariate analysis indicated that plasma MMP-9 activity was not predicted by the known clinicopathological parameters such as age, stage, tumor size, number of positive lymph nodes, histologic grade, histologic type, nuclear grade or mitotic index. Lung cancer patients also presented high values of MMP-9 (Md 1.43, range 0.0–3.6 [n = 26]), without association with tumor stage or histologic type. The levels of 92 kDa-MMP activity in the plasma euglobulin fraction could be a potentially useful tumor marker in breast and lung cancer.Fil: Farias, Eduardo Francisco. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ranuncolo, Stella Maris. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cresta Morgado, Carlos. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Specterman, Sergio. Hospital Italiano; ArgentinaFil: Armanasco, Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Varela, Mirta. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lastiri, José. Hospital Italiano; ArgentinaFil: Pallotta, María Guadalupe. Hospital Italiano; ArgentinaFil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Puricelli, Lydia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentin

Lymphotropic viruses EBV, KSHV and HTLV in Latin America: Epidemiology and associated malignancies. A literature-based study by the RIAL-CYTED

The Epstein-Barr virus (EBV), Kaposi sarcoma herpesvirus (KSHV) and human T-lymphotropic virus (HTLV-1) are lymphomagenic viruses with region-specific induced morbidity. The RIAL-CYTED aims to increase the knowledge of lymphoma in Latin America (LA), and, as such, we systematically analyzed the literature to better understand our risk for virus-induced lymphoma. We observed that high endemicity regions for certain lymphomas, e.g., Mexico and Peru, have a high incidence of EBV-positive lymphomas of T/NK cell origin. Peru also carries the highest frequency of EBV-positive classical Hodgkin lymphoma (HL) and EBV-positive diffuse large B cell lymphoma, not otherwise specified (NOS), than any other LA country. Adult T cell lymphoma is endemic to the North of Brazil and Chile. While only few cases of KSHV-positive lymphomas were found, in spite of the close correlation of Kaposi sarcoma and the prevalence of pathogenic types of KSHV. Both EBV-associated HL and Burkitt lymphoma mainly affect young children, unlike in developed countries, in which adolescents and young adults are the most affected, correlating with an early EBV seroconversion for LA population despite of lack of infectious mononucleosis symptoms. High endemicity of KSHV and HTLV infection was observed among Amerindian populations, with differences between Amazonian and Andean populations.Fil: Chabay, Paola Andrea. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Lens, Daniela. Universidad de la Republica. Facultad de Medicina. Hospital de Clínicas "dr. Manuel Quintela".; UruguayFil: Hassan, Rocio. National Cancer Institute “José Alencar Gomes da Silva”; BrasilFil: Rodríguez Pinilla, Socorro María. University Hospital, Fundación Jiménez Díaz; EspañaFil: Valvert Gamboa, Fabiola. Cancer Institute and National League against Cancer; GuatemalaFil: Rivera, Iris. Salvadoran Institute of Social Security; El SalvadorFil: Huamán Garaicoa, Fuad. Santiago de Guayaquil Catholic University; EcuadorFil: Ranuncolo, Stella Maris. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barrionuevo, Carlos. National University of San Marcos; PerúFil: Morales Sánchez, Abigail. Children’s Hospital of Mexico Federico Gómez; MéxicoFil: Scholl, Vanesa. No especifíca;Fil: de Matteo, Elena Noemí. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Fuentes Pananá, Ezequiel M.. Children’s Hospital of Mexico Federico Gómez; Méxic

Towards the dreamed biomarkers?

Detection and determination of tumor biomarkers are made from tissue and blood collection. During the last decade new biological sources are feasible: circulating tumor cells and circulating nucleic acids. They are composing a new field named as liquid biopsy. The availability of next-generation sequencing and Digital-PCR among other techniques, led to the possibility of getting the most out of this “circulating material” that would mirror the genetic and epigenetic features of the tumor.Fil: Ranuncolo, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Universidad de Buenos Aires; Argentin

Interferencia del brazo alternativo de NFkB y bloqueo de BCL2 como potenciales blancos terapèuticos en el Linfoma de Hodgkin clásico

El brazo alternativo de NFkB exhibe un rol importante en la supervivencia de las células de Linfoma de Hodgkin clásico (cLH). Nuestros resultados previos mostraron la expresión de NIK (Kinasa Inductora de NFkB) y de BCL2 (uno de los principales genes controlados por esta vía de señalización) en las biopsias de pacientes con cLH. Reportamos que la expresión de BCL2 en las células de Hodgkin y Reed Sternberg, en las biopsias de pacientes con cLH al diagnóstico de la enfermedad primaria, resulta de utilidad como marcador de pronóstico. El objetivo de la data incluida en esta sección fue determinar los efectos del inhibidor de NIK (4H-isoquinolina-1,3-diona) y del bloqueante de BCL2 (venetoclax) como monodrogas y como terapia combinada en la línea celular L1236.Fil: Díaz, Mariángeles. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ranuncolo, Stella Maris. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Alternative and canonical NF-kB pathways DNA-binding hierarchies networks define Hodgkin lymphoma and Non-Hodgkin diffuse large B Cell lymphoma respectively

Purpose: Despite considerable evidence that supports the NF-kB role in the immune system and lymphomagenesis, it is unclear whether specific NF-kB dimers control a particular set of genes that account for their biological functions. Our previous work showed that Hodgkin Lymphoma (HL) is unique, among germinal center (GC)-derived lymphomas, with respect to its dependency on Rel-B to survive. In contrast, diffuse large B-Cell lymphoma (DLBCL) including both Activated B-Cell-Like and Germinal Center B-Cell-Like, requires cREL and Rel-A to survive and it is not affected by Rel-B depletion. These findings highlighted the activity of specific NF-kB subunits in different GC-derived lymphomas. Methods: Sequenced chromatin immunoprecipitated DNA fragments (ChIP-Seq) analysis revealed an extensive NF-kB DNA-binding network in DLBCL and HL. The ChIP-Seq data was merged with microarray analysis following the Rel-A, Rel-B or cRel knockdown to determine effectively regulated genes. Results: Downstream target analysis showed enrichment for cell cycle control, among other signatures. Rel-B and cRel controlled different genes within the same signature in HL and DLBCL, respectively. BCL2 was exclusively controlled by Rel-B in HL. Both mRNA and protein levels decreased following Rel-B depletion meanwhile there was no change upon cRel knock-down. BCL2 exogenous expression partially rescued the death induced by decreased Rel-B in HL cells. Conclusion: The Rel-B hierarchical network defined HL and the cRel hierarchical network characterized DLBCL. Each Rel member performs specific functions in distinct GC-derived lymphomas. This result should be considered for the development of targeted therapies that are aimed to selectively inhibit individual NF-kB dimers.Fil: Gamboa Cedeño, Angélica María. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Castillo, Mariángeles. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Wenming, Xiao. National Institutes of Health; Estados UnidosFil: Waldmann, Thomas. National Institutes of Health; Estados UnidosFil: Ranuncolo, Stella Maris. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; Argentin

Circulating Fibroblast Growth Factor 21 (Fgf21) as Diagnostic and Prognostic Biomarker in Renal Cancer

Background: The finding of new biomarkers is needed to have a better sub-classification of primary renal tumors (RCC) as well as more reliable predictors of outcome and therapy response. In this study, we evaluated the role of circulating FGF21, an endocrine factor, as a diagnostic and prognostic biomarker for ccRCC.Materials and Methods: Serum samples from healthy controls (HC), clear cell and chromophobe RCC cancer patients were obtained from the serum biobank ?Biobanco Público de Muestras Séricas Oncológicas? (BPMSO)of the ?Instituto de Oncología ?Ángel H. Roffo?. Serum FGF21 and leptin were measured by ELISA while other metabolic markers were measured following routinely clinical procedures.Results: One of our major findings was that FGF21 levels were significantly increased in ccRCC patients compared with HC. Moreover, we showed an association between the increased serum FGF21 levels and theshorter disease free survival in a cohort of 98 ccRCC patients, after adjustment for other predictors of outcome.Conclusion: Our results suggest that higher FGF21 serum level is an independent prognostic biomarker, associated with worse free-disease survival.Fil: Knott, María Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Minatta, J.N. Hospital Italiano; ArgentinaFil: Roulet, L.. Hospital Italiano; ArgentinaFil: Gueglio G.. Hospital Italiano; ArgentinaFil: Pasik, Leonardo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Ranuncolo, Stella Maris. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nuñez, M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Puricelli, Lydia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: De Lorenzo, M. New Jersey Medical School; Estados Unido

Apoptotic regulator BCL-2 blockade aS a potential therapy in classical Hodgkin Lymphoma

The challenge in classical Hodgkin Lymphoma (cHL) management is the 30–40% of refractory/relapsed cases. Aims: The aim of this work was to determine whether NIK and BCL-2 could be useful as prognosis biomarkers in cHL. In addition, we evaluated BCL-2 as a directed-therapy in cHL cell lines using venetoclax. Main methods: We evaluated NIK and BCL-2 expression in 112 untreated cHL patients' lymph-node biopsies by immunohistochemistry. cHL cell lines were treated with venetoclax alone or combined with vincristine or doxorubicin. Cell viability, metabolic activity and cell death were analyzed by trypan-blue exclusion method, MTS assay and FDA/IP staining respectively. Key findings: No correlation between NIK or BCL-2 expression and the majority of the clinical parameters was found. Patients with ≥60% BCL-2+ HRS-cells had a shorter disease-free survival (DFS) and overall survival (OS) (p = 0.002, p = 0.02 respectively). A decision tree analysis, in a 30 patients subgroup, showed that patients with <60% NIK+ HRS-cells but with ≥60% BCL-2+ HRS-cells had a worse outcome in terms of DFS and OS. These parameters performed better as prognosis indicators as compared to the diagnosis bone marrow status. Human cHL cell lines U-H01, KM-H2, L1236, SUPHD1, L540 showed sensitivity to venetoclax. The co-treatment effect of venetoclax and vincristine or doxorubicin on cell viability was diverse depending on the cell line evaluated. Significance: BCL-2 should be considered as a prognosis biomarker as well as a potential new therapeutic target in cHL. We report for the first time the cytotoxic effect of venetoclax in human cHL cell lines.Fil: Gamboa Cedeño, Angélica María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaFil: Díaz, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Cristaldo, Nancy. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Otero, Victoria. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Schutz, Natalia. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Fantl, Dorotea. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Cugliari, María Silvana. Universidad de Buenos Aires; ArgentinaFil: Zerga, Marta Elisa. Universidad de Buenos Aires; ArgentinaFil: Rojas Bilbao, Érica. Universidad de Buenos Aires; ArgentinaFil: Jauk, Federico. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan Jorge. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Núñez, Myriam Carmen. Universidad de Buenos Aires; ArgentinaFil: Ranuncolo, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentin

Related F-­box proteins control cell death in Caenorhabditis elegans and human lymphoma

Cell death is a common metazoan cell fate, and its inactivation is central to human malignancy. In Caenorhabditis elegans, apoptotic cell death occurs via the activation of the caspase CED-3 following binding of the EGL-1/BH3-only protein to the antiapoptotic CED-9/ BCL2 protein. Here we report a major alternative mechanism for caspase activation in vivo involving the F-box protein DRE-1. DRE-1 functions in parallel to EGL-1, requires CED-9 for activity, and binds to CED-9, suggesting that DRE-1 promotes apoptosis by inactivating CED-9. FBXO10, a human protein related to DRE-1, binds BCL2 and promotes its degradation, thereby initiating cell death. Moreover, some human diffuse large B-cell lymphomas have inactivating mutations in FBXO10 or express FBXO10 at low levels. Our results suggest that DRE-1/FBXO10 is a conserved regulator of apoptosis.Fil: Chiorazzi, Michael. The Rockefeller University. Laboratory of Developmental Genetics; Estados Unidos de América;Fil: Rui, Lixin. National Cancer Institute. Center for Cancer Research. Metabolism Branch; Estados Unidos de América;Fil: Yang, Yandan. National Cancer Institute. Center for Cancer Research. Metabolism Branch; Estados Unidos de América;Fil: Ceribelli, Michelle. National Cancer Institute. Center for Cancer Research. Metabolism Branch; Estados Unidos de América;Fil: Tishbi, Nima. The Rockefeller University. Laboratory of Developmental Genetics; Estados Unidos de América;Fil: Maurer. Carine W.. The Rockefeller University. Laboratory of Developmental Genetics; Estados Unidos de América;Fil: Ranuncolo, Stella Maris. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; National Cancer Institute. Center for Cancer Research. Metabolism Branch; Estados Unidos de América; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Zhao, Hong. National Cancer Institute. Center for Cancer Research. Metabolism Branch; Estados Unidos de América;Fil: Xu, Weihong. National Cancer Institute. Center for Cancer Research. Metabolism Branch; Estados Unidos de América;Fil: Chan, Wing-Chung C.. University of Nebraska. Department of Pathology and Microbiology; Estados Unidos de América;Fil: Jaffe, Elaine S.. National Cancer Institute. Center for Cancer Research. Laboratory of Pathology; Estados Unidos de América;Fil: Gascoyne, Randy D.. British Columbia Cancer Agency; Canadá;Fil: Campo, Elias. Universidad de Barcelona. Hospital Clínico; España;Fil: Rossenwald, Andreas. University of Wurzburg. Department of Pathology; Alemania;Fil: Ott, German. Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology. Department of Clinical Pathology; Alemania;Fil: Delabie, Jan. Oslo University Hospital. Pathology Clinic; Noruega;Fil: Rimsza, Lisa M.. University of Arizona. Department of Pathology; Estados Unidos de América; Southwest Oncology Group; Estados Unidos de América;Fil: Shaham, Shai. The Rockefeller University. Laboratory of Developmental Genetics; Estados Unidos de América;Fil: Staudt, Louis M.. National Cancer Institute. Center for Cancer Research. Metabolism Branch; Estados Unidos de América