TY - JOUR
T1 - Genome-wide mutational signatures revealed distinct developmental paths for human B cell lymphomas
AU - Ye, Xiaofei
AU - Ren, Weicheng
AU - Liu, Dongbing
AU - Li, Xiaobo
AU - Li, Wei
AU - Wang, Xianhuo
AU - Meng, Fei Long
AU - Yeap, Leng Siew
AU - Hou, Yong
AU - Zhu, Shida
AU - Casellas, Rafael
AU - Zhang, Huilai
AU - Wu, Kui
AU - Pan-Hammarström, Qiang
N1 - Funding Information:
This work was supported by Cancerfonden (Swedish Cancer Society), the Swedish Research Council, the Swedish Childhood Cancer fund, the National Natural Science Foundation of China (81670184), the Joint Research Initiative of the School of Medicine, Shanghai Jiao Tong University, the Radiumhemmet research fund, the Center for Innovative Medicine, the Guangdong Enterprise Key Laboratory of Human Disease Genomics (2020B1212070028), and the China National GeneBank.
Publisher Copyright:
© 2020 Ye et al.
PY - 2021/2
Y1 - 2021/2
N2 - Both somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytidine deaminase (AID). Dysregulation of these processes has been linked to B cell lymphomagenesis. Here we performed an in-depth analysis of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) genomes. We characterized seven genomic mutational signatures, including two B cell tumor-specific signatures, one of which is novel and associated with aberrant SHM. We further identified two major mutational signatures (K1 and K2) of clustered mutations (kataegis) resulting from the activities of AID or error-prone DNA polymerase η, respectively. K1 was associated with the immunoglobulin (Ig) switch region mutations/translocations and the ABC subtype of DLBCL, whereas K2 was related to the Ig variable region mutations and the GCB subtype of DLBCL and FL. Similar patterns were also observed in chronic lymphocytic leukemia subtypes. Thus, alterations associated with aberrant CSR and SHM activities can be linked to distinct developmental paths for different subtypes of B cell lymphomas.
AB - Both somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytidine deaminase (AID). Dysregulation of these processes has been linked to B cell lymphomagenesis. Here we performed an in-depth analysis of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) genomes. We characterized seven genomic mutational signatures, including two B cell tumor-specific signatures, one of which is novel and associated with aberrant SHM. We further identified two major mutational signatures (K1 and K2) of clustered mutations (kataegis) resulting from the activities of AID or error-prone DNA polymerase η, respectively. K1 was associated with the immunoglobulin (Ig) switch region mutations/translocations and the ABC subtype of DLBCL, whereas K2 was related to the Ig variable region mutations and the GCB subtype of DLBCL and FL. Similar patterns were also observed in chronic lymphocytic leukemia subtypes. Thus, alterations associated with aberrant CSR and SHM activities can be linked to distinct developmental paths for different subtypes of B cell lymphomas.
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U2 - 10.1084/JEM.20200573
DO - 10.1084/JEM.20200573
M3 - Article
C2 - 33136155
AN - SCOPUS:85095402294
SN - 0022-1007
VL - 218
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
M1 - e20200573
ER -