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Sökning: id:"swepub:oai:DiVA.org:uu-532555" > Genetic Characteriz...

Genetic Characterization of Primary Mediastinal B-Cell Lymphoma : Pathogenesis and Patient Outcomes

Noerenberg, Daniel (författare)
Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Campus Virchow,Augustenburger Pl 1, D-13353 Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.
Briest, Franziska (författare)
Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Campus Virchow,Augustenburger Pl 1, D-13353 Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.
Hennch, Cornelius (författare)
Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Campus Virchow,Augustenburger Pl 1, D-13353 Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.
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Yoshida, Kenichi (författare)
Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan.;Natl Canc Ctr, Div Canc Evolut, Tokyo, Japan.
Hablesreiter, Raphael (författare)
Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Campus Virchow,Augustenburger Pl 1, D-13353 Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.
Takeuchi, Yasuhide (författare)
Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan.
Ueno, Hiroo (författare)
Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan.
Staiger, Annette M. (författare)
Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.;Dr Margarete Fischer Bosch Inst Clin Pharmacol Stu, Stuttgart, Germany.;Univ Tubingen, Stuttgart, Germany.
Ziepert, Marita (författare)
Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.
Asmar, Fazila (författare)
Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark.
Locher, Benjamin N. (författare)
Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Campus Virchow,Augustenburger Pl 1, D-13353 Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.
Toth, Erika (författare)
Natl Inst Oncol, Dept Surg & Mol Pathol, Natl Tumour Biol Lab, Budapest, Hungary.
Weber, Thomas (författare)
Martin Luther Univ Halle Wittenberg, Univ Hosp Halle Saale, Dept Internal Med Haematol & Oncol 4, Halle, Germany.
Amini, Rose-Marie (författare)
Uppsala universitet,Cancerimmunterapi,Univ Hosp, Uppsala, Sweden
Klapper, Wolfram (författare)
Univ Klinikum Schleswig Holstein, Dept Pathol, Hematopathol Sect & Lymph Node Registry, Kiel, Germany.
Bouzani, Maria (författare)
Evaggelismos Gen Hosp, BMTU, Dept Hematol & Lymphoma, Athens, Greece.
Poeschel, Viola (författare)
Saarland Univ, Med Sch, Dept Internal Med Oncol Hematol Clin Immunol & Rhe, Homburg, Germany.
Rosenwald, Andreas (författare)
Univ Wurzburg, Inst Pathol, Wurzburg, Germany.;Comprehens Canc Ctr CCC Mainfranken, Wurzburg, Germany.
Held, Gerhard (författare)
Saarland Univ, Med Sch, Dept Internal Med Oncol Hematol Clin Immunol & Rhe, Homburg, Germany.;Westpfalzklinikum Kaiserslautern, Dept Internal Med I, Kaiserslautern, Germany.
Campo, Elias (författare)
Ctr Invest Biomed Red Oncol CIBERONC, Madrid, Spain.;Univ Barcelona, Hosp Clin Barcelona, Barcelona, Spain.;Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.
Ishaque, Naveed (författare)
Charite Univ Med Berlin, Berlin Inst Hlth, Ctr Digital Hlth, Berlin, Germany.
Stamatopoulos, Kostas (författare)
Karolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
Kanellis, George (författare)
Evangelismos Gen Hosp, Dept Hematopathol, Athens, Greece.
Anagnostopoulos, Ioannis (författare)
Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.;Univ Wurzburg, Inst Pathol, Wurzburg, Germany.;Comprehens Canc Ctr CCC Mainfranken, Wurzburg, Germany.;Charite Univ Med Berlin, Dept Pathol, Berlin, Germany.
Bullinger, Lars (författare)
Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Campus Virchow,Augustenburger Pl 1, D-13353 Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.;German Canc Consortium DKTK, Heidelberg, Germany.
Goldschmidt, Neta (författare)
Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel.
Zinzani, Pier Luigi (författare)
IRCCS Azienda Osped Univ Bologna, Ist Ematol Seragnoli, Bologna, Italy.;Univ Bologna, Dipartimento Med Specialist Diag & Sperimentale, Bologna, Italy.
Bödör, Csaba (författare)
Semmelweis Univ, Dept Pathol & Expt Canc Res 1, HCEMM SE Mol Oncohematol Res Grp, Budapest, Hungary.
Rosenquist, Richard (författare)
Karolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Genet, Stockholm, Sweden.
Vassilakopoulos, Theodoros P. (författare)
Martin Luther Univ Halle Wittenberg, Univ Hosp Halle Saale, Dept Internal Med Haematol & Oncol 4, Halle, Germany.;Natl & Kapodistrian Univ Athens, Laikon Gen Hosp, Dept Hematol & Bone Marrow Transplantat, Athens, Greece.
Ott, German (författare)
Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
Ogawa, Seishi (författare)
Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan.;Karolinska Inst, Ctr Haematol & Regenerat Med, Dept Med, Stockholm, Sweden.;Kyoto Univ, Inst Adv Study Human Biol WPI ASHBi, Kyoto, Japan.
Damm, Frederik (författare)
Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Campus Virchow,Augustenburger Pl 1, D-13353 Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.;German Canc Consortium DKTK, Heidelberg, Germany.
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Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Campus Virchow,Augustenburger Pl 1, D-13353 Berlin, Germany;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany. Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan.;Natl Canc Ctr, Div Canc Evolut, Tokyo, Japan. (creator_code:org_t)
American Society of Clinical Oncology (ASCO), 2024
2024
Engelska.
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 42:4, s. 452-466
Relaterad länk:
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • PurposePrimary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive lymphoma predominantly affecting young female patients. Large-scale genomic investigations and genetic markers for risk stratification are lacking.Patients and MethodsTo elucidate the full spectrum of genomic alterations, samples from 340 patients with previously untreated PMBCL were investigated by whole-genome (n = 20), whole-exome (n = 78), and targeted (n = 308) sequencing. Statistically significant prognostic variables were identified using a multivariable Cox regression model and confirmed by L1/L2 regularized regressions.ResultsWhole-genome sequencing revealed a commonly disrupted p53 pathway with nonredundant somatic structural variations (SVs) in TP53-related genes (TP63, TP73, and WWOX) and identified novel SVs facilitating immune evasion (DOCK8 and CD83). Integration of mutation and copy-number data expanded the repertoire of known PMBCL alterations (eg, ARID1A, P2RY8, and PLXNC1) with a previously unrecognized role for epigenetic/chromatin modifiers. Multivariable analysis identified six genetic lesions with significant prognostic impact. CD58 mutations (31%) showed the strongest association with worse PFS (hazard ratio [HR], 2.52 [95% CI, 1.50 to 4.21]; P < .001) and overall survival (HR, 2.33 [95% CI, 1.14 to 4.76]; P = .02). IPI high-risk patients with mutated CD58 demonstrated a particularly poor prognosis, with 5-year PFS and OS rates of 41% and 58%, respectively. The adverse prognostic significance of the CD58 mutation status was predominantly observed in patients treated with nonintensified regimens, indicating that dose intensification may, to some extent, mitigate the impact of this high-risk marker. By contrast, DUSP2-mutated patients (24%) displayed durable responses (PFS: HR, 0.2 [95% CI, 0.07 to 0.55]; P = .002) and prolonged OS (HR, 0.11 [95% CI, 0.01 to 0.78]; P = .028). Upon CHOP-like treatment, these patients had very favorable outcome, with 5-year PFS and OS rates of 93% and 98%, respectively.ConclusionThis large-scale genomic characterization of PMBCL identified novel treatment targets and genetic lesions for refined risk stratification. DUSP2 and CD58 mutation analyses may guide treatment decisions between rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

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