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Clonally unrelated Richter syndrome are truly de novo diffuse large B‐cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome
Author(s) -
Favini Chiara,
Talotta Donatella,
Almasri Mohammad,
Andorno Annalisa,
Rasi Silvia,
Adhinaveni Ramesh,
Kogila Sreekar,
Awikeh Bassel,
Schipani Mattia,
Boggione Paola,
Mouhssine Samir,
Ghanej Joseph,
Al Essa Wael,
Mahmoud Abdurraouf Mokhtar,
Dondolin Riccardo,
Alessa Nariman,
Margiotta Casaluci Gloria,
Boldorini Renzo,
Gattei Valter,
Gaidano Gianluca,
Moia Riccardo
Publication year - 2022
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.18352
Subject(s) - ighv@ , clone (java method) , biology , lymphoma , chronic lymphocytic leukemia , diffuse large b cell lymphoma , immunoglobulin heavy chain , gene rearrangement , cancer research , somatic evolution in cancer , genetics , gene , immunology , leukemia
Summary Richter syndrome (RS) is mostly due to the direct transformation of the chronic lymphocytic leukaemia (CLL) clone, as documented by the same immunoglobulin heavy‐chain variable region (IGHV) rearrangement in both CLL and RS cells. In rare cases characterized by a better outcome, the RS clone harbours a different IGHV rearrangement compared to the CLL phase. We investigated the CLL phase of clonally unrelated RS to test whether the RS clone was already identifiable prior to clinicopathologic transformation, albeit undetectable by conventional approaches. CLL cells of eight patients with unrelated RS were subjected to an ultra‐deep next‐generation sequencing (NGS) approach with a sensitivity of 10 −6 . In 7/8 cases, the RS rearrangement was not identified in the CLL phase. In one case, the RS clone was identified at a very low frequency in the CLL phase, conceivably due to the concomitance of CLL sampling and RS diagnosis. Targeted resequencing revealed that clonally unrelated RS carries genetic lesions primarily affecting the TP53 , MYC , ATM and NOTCH1 genes. Conversely, mutations frequently involved in de novo diffuse large B‐cell lymphoma (DLBCL) without a history of CLL were absent. These results suggest that clonally unrelated RS is a truly de novo lymphoma with a mutational profile reminiscent, at least in part, of clonally related RS.