BCL2 mutation spectrum in B-cell non-Hodgkin lymphomas and patterns associated with evolution of follicular lymphoma

Burkhard, Regula; Bhagat, Govind; Cogliatti, Sergio B; Rossi, Davide; Gaidano, Gianluca; Pasqualucci, Laura; Novak, Urban (2014). BCL2 mutation spectrum in B-cell non-Hodgkin lymphomas and patterns associated with evolution of follicular lymphoma. Hematological oncology, 33(1), pp. 23-30. Wiley 10.1002/hon.2132

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BCL2 is a target of somatic hypermutation in t(14;18) positive and also in a small fraction of t(14;18) negative diffuse large B-cell lymphoma (DLBCL), suggesting an aberrant role of somatic hypermutation (ASHM). To elucidate the prevalence of BCL2 mutations in lymphomas other than DLBCL, we Sanger-sequenced the hypermutable region of the BCL2 gene in a panel of 69 mature B-cell lymphomas, including Richter's syndrome DLBCL, marginal-zone lymphomas, post-transplant lymphoproliferative disorders, HIV-associated and common-variable immunodeficiency-associated DLBCL, all known to harbour ASHM-dependent mutations in other genes, as well as 16 t(14,18) negative and 21 t(14;18) positive follicular lymphomas (FLs). We also investigated the pattern of BCL2 mutations in longitudinal samples from 10 FL patients relapsing to FL or transforming to DLBCL (tFL). By direct sequencing, we found clonally represented BCL2 mutations in 2/16 (13%) of t(14;18) negative FLs, 2/16 (13%) HIV-DLBCLs, 1/9 (11%) of Richter's syndrome DLBCL, 1/17 (6%) of post-transplant lymphoproliferative disorders and 1/2 (50%) common-variable immunodeficiency-associated DLBCL. The proportion of mutated cases was significantly lower than in FLs carrying the t(14;18) translocation (15/21, 71%). However, the absence of t(14;18) by FISH or PCR and the molecular features of the mutations strongly suggest that BCL2 represents an additional target of ASHM in these entities. Analysis of the BCL2 mutation pattern in clonally related FL/FL and FL/tFL samples revealed two distinct scenarios of genomic evolution: (i) direct evolution from the antecedent FL clone, with few novel clonal mutations acquired by the tFL major clone, and (ii) evolution from a common mutated long-lived progenitor cell, which subsequently acquired distinct mutations in the FL and in the relapsed or transformed counterpart. Copyright © 2014 John Wiley & Sons, Ltd.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.)

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Burkhard, Regula and Novak, Urban

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1099-1069

Publisher:

Wiley

Language:

English

Submitter:

Monique Ryter

Date Deposited:

10 Feb 2015 13:50

Last Modified:

26 Jun 2016 01:58

Publisher DOI:

10.1002/hon.2132

PubMed ID:

24496723

Uncontrolled Keywords:

(aberrant) somatic hypermutation, BCL2, clonal evolution, diffuse large B-cell lymphoma, follicular lymphoma

BORIS DOI:

10.7892/boris.62876

URI:

https://boris.unibe.ch/id/eprint/62876

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