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Genetic evolution of in situ follicular neoplasia to aggressive B-cell lymphoma of germinal center subtype.
Vogelsberg, Antonio; Steinhilber, Julia; Mankel, Barbara; Federmann, Birgit; Schmidt, Janine; Montes-Mojarro, Ivonne A; Hüttl, Katrin; Rodriguez-Pinilla, Maria; Baskaran, Praveen; Nahnsen, Sven; Piris, Miguel A; Ott, German; Quintanilla-Martinez, Leticia; Bonzheim, Irina; Fend, Falko.
Afiliación
  • Vogelsberg A; Institute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
  • Steinhilber J; Institute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
  • Mankel B; Institute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
  • Federmann B; Institute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
  • Schmidt J; Institute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
  • Montes-Mojarro IA; Institute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
  • Hüttl K; Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
  • Rodriguez-Pinilla M; Department of Pathology, Fundación Jiménez Díaz, Madrid, Spain.
  • Baskaran P; Quantitative Biology Center, University of Tuebingen, Tuebingen, Germany.
  • Nahnsen S; Quantitative Biology Center, University of Tuebingen, Tuebingen, Germany.
  • Piris MA; Department of Pathology, Fundación Jiménez Díaz, Madrid, Spain.
  • Ott G; Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
  • Quintanilla-Martinez L; Institute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
  • Bonzheim I; Institute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
  • Fend F; Institute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
Haematologica ; 106(10): 2673-2681, 2021 10 01.
Article en En | MEDLINE | ID: mdl-32855278
In situ follicular neoplasia (ISFN) is the earliest morphologically identifiable precursor of follicular lymphoma (FL). Although it is genetically less complex than FL and has low risk for progression, ISFN already harbors secondary genetic alterations, in addition to the defining t(14;18)(q32;q21) translocation. FL, in turn, frequently progresses to diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL). By BCL2 staining of available reactive lymphoid tissue obtained at any time point in patients with aggressive B-cell lymphoma (BCL), we identified ten paired cases of ISFN and DLBCL/HGBL, including six de novo tumors and four tumors transformed from FL as an intermediate step, and investigated their clonal evolution using microdissection and next-generation sequencing. A clonal relationship between ISFN and aggressive BCL was established by immunoglobulin and/or BCL2 rearrangements and/or the demonstration of shared somatic mutations for all ten cases. Targeted sequencing revealed CREBBP, KMT2D, EZH2, TNFRSF14 and BCL2 as the genes most frequently mutated already in ISFN. Based on the distribution of private and shared mutations, two patterns of clonal evolution were evident. In most cases, the aggressive lymphoma, ISFN and, when present, FL revealed divergent evolution from a common progenitor, whereas linear evolution with sequential accumulation of mutations was less frequent. In conclusion, we demonstrate for the first time that t(14;18)+ aggressive BCL can arise from ISFN without clinically evident FL as an intermediate step and that during this progression, branched evolution is common.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma Folicular / Linfoma de Células B Grandes Difuso Límite: Humans Idioma: En Revista: Haematologica Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Italia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma Folicular / Linfoma de Células B Grandes Difuso Límite: Humans Idioma: En Revista: Haematologica Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Italia