Genomic characterization of lymphomas in patients with inborn errors of immunity.
Genomic characterization of lymphomas in patients with inborn errors of immunity.
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DOI：
10.1182/bloodadvances.2021006654
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发表时间：
2022-09-27
期刊：
影响因子：
7.5
通讯作者：
Pan-Hammarstrom, Qiang
中科院分区：
文献类型：
--
作者：
Ye, Xiaofei;Maglione, Paul J.;Wehr, Claudia;Li, Xiaobo;Wang, Yating;Abolhassani, Hassan;Deripapa, Elena;Liu, Dongbing;Borte, Stephan;Du, Likun;Wan, Hui;Ploetner, Andreas;Giannoula, Yvonne;Ko, Huai-Bin;Hou, Yong;Zhu, Shida;Grossman, Jennifer K.;Sander, Birgitta;Grimbacher, Bodo;Hammarstrom, Lennart;Fedorova, Alina;Rosenzweig, Sergio D.;Shcherbina, Anna;Wu, Kui;Warnatz, Klaus;Cunningham-Rundles, Charlotte;Pan-Hammarstrom, Qiang
免疫相关淋巴瘤的先天性错误具有明显的临床特征和遗传特征。生殖系和体细胞改变都有助于先天性免疫错误患者的淋巴瘤发生。先天性免疫缺陷（IEI）患者患癌症的风险更高，尤其是淋巴瘤。然而，iei相关淋巴瘤的分子基础是复杂的，仍然难以捉摸。在这里，我们对23名IEI患者的淋巴瘤基因组进行了深入分析。我们鉴定并验证了23例患者中14例的致病或相关种系突变，包括ATM、BACH2、BLM、CD70、G6PD、NBN、PIK3CD、PTEN和TNFRSF13B。此外，我们分析了淋巴瘤基因组中的体细胞突变，并确定了8个基因在iei相关弥漫性大b细胞淋巴瘤（DLBCLs）中的突变水平显著高于非iei DLBCLs，如BRCA2， NCOR1, KLF2， FAS， CCND3和BRWD3。后者BRWD3在活化磷酸肌肽3-激酶δ综合征患者的肿瘤亚组中优先发生突变。我们还在iei相关的淋巴瘤中发现了5个基因组突变特征，包括2个DNA修复缺陷相关的特征，并且在布鲁姆综合征患者的肿瘤基因组中发现了数量惊人的染色体间和染色体内结构变异。总之，我们对来自罕见遗传疾病患者的淋巴瘤的全面基因组表征扩展了我们对淋巴瘤发生的理解，并为靶向治疗提供了新的见解。
Inborn errors of immunity-associated lymphomas are characterized by distinct clinical features and genetic signatures. Both germline and somatic alterations contribute to lymphomagenesis in patients with inborn errors of immunity. Patients with inborn errors of immunity (IEI) have a higher risk of developing cancer, especially lymphoma. However, the molecular basis for IEI-related lymphoma is complex and remains elusive. Here, we perform an in-depth analysis of lymphoma genomes derived from 23 IEI patients. We identified and validated disease-causing or -associated germline mutations in 14 of 23 patients involving ATM, BACH2, BLM, CD70, G6PD, NBN, PIK3CD, PTEN, and TNFRSF13B. Furthermore, we profiled somatic mutations in the lymphoma genome and identified 8 genes that were mutated at a significantly higher level in IEI-associated diffuse large B-cell lymphomas (DLBCLs) than in non-IEI DLBCLs, such as BRCA2, NCOR1, KLF2, FAS, CCND3, and BRWD3. The latter, BRWD3, is furthermore preferentially mutated in tumors of a subgroup of activated phosphoinositide 3-kinase δ syndrome patients. We also identified 5 genomic mutational signatures, including 2 DNA repair deficiency-related signatures, in IEI-associated lymphomas and a strikingly high number of inter- and intrachromosomal structural variants in the tumor genome of a Bloom syndrome patient. In summary, our comprehensive genomic characterization of lymphomas derived from patients with rare genetic disorders expands our understanding of lymphomagenesis and provides new insights for targeted therapy.
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影响因子：
30.5
作者：
Afzali B;Grönholm J;Vandrovcova J;O'Brien C;Sun HW;Vanderleyden I;Davis FP;Khoder A;Zhang Y;Hegazy AN;Villarino AV;Palmer IW;Kaufman J;Watts NR;Kazemian M;Kamenyeva O;Keith J;Sayed A;Kasperaviciute D;Mueller M;Hughes JD;Fuss IJ;Sadiyah MF;Montgomery-Recht K;McElwee J;Restifo NP;Strober W;Linterman MA;Wingfield PT;Uhlig HH;Roychoudhuri R;Aitman TJ;Kelleher P;Lenardo MJ;O'Shea JJ;Cooper N;Laurence ADJ
通讯作者：
Laurence ADJ
影响因子：
9.8
作者：
Field, Michael;Tarpey, Patrick S.;Raymond, F. Lucy
通讯作者：
Raymond, F. Lucy
DOI：
10.1084/jem.20100244
发表时间：
2010-04-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bothmer A;Robbiani DF;Feldhahn N;Gazumyan A;Nussenzweig A;Nussenzweig MC
通讯作者：
Nussenzweig MC
全基因组关联研究确定了弥漫性大B细胞淋巴瘤的多个易感基因座。
影响因子：
30.8
作者：
Cerhan JR;Berndt SI;Vijai J;Ghesquières H;McKay J;Wang SS;Wang Z;Yeager M;Conde L;de Bakker PI;Nieters A;Cox D;Burdett L;Monnereau A;Flowers CR;De Roos AJ;Brooks-Wilson AR;Lan Q;Severi G;Melbye M;Gu J;Jackson RD;Kane E;Teras LR;Purdue MP;Vajdic CM;Spinelli JJ;Giles GG;Albanes D;Kelly RS;Zucca M;Bertrand KA;Zeleniuch-Jacquotte A;Lawrence C;Hutchinson A;Zhi D;Habermann TM;Link BK;Novak AJ;Dogan A;Asmann YW;Liebow M;Thompson CA;Ansell SM;Witzig TE;Weiner GJ;Veron AS;Zelenika D;Tilly H;Haioun C;Molina TJ;Hjalgrim H;Glimelius B;Adami HO;Bracci PM;Riby J;Smith MT;Holly EA;Cozen W;Hartge P;Morton LM;Severson RK;Tinker LF;North KE;Becker N;Benavente Y;Boffetta P;Brennan P;Foretova L;Maynadie M;Staines A;Lightfoot T;Crouch S;Smith A;Roman E;Diver WR;Offit K;Zelenetz A;Klein RJ;Villano DJ;Zheng T;Zhang Y;Holford TR;Kricker A;Turner J;Southey MC;Clavel J;Virtamo J;Weinstein S;Riboli E;Vineis P;Kaaks R;Trichopoulos D;Vermeulen RC;Boeing H;Tjonneland A;Angelucci E;Di Lollo S;Rais M;Birmann BM;Laden F;Giovannucci E;Kraft P;Huang J;Ma B;Ye Y;Chiu BC;Sampson J;Liang L;Park JH;Chung CC;Weisenburger DD;Chatterjee N;Fraumeni JF Jr;Slager SL;Wu X;de Sanjose S;Smedby KE;Salles G;Skibola CF;Rothman N;Chanock SJ
通讯作者：
Chanock SJ
DOI：
10.1073/pnas.1418947112
发表时间：
2015-02-17
影响因子：
11.1
作者：
Bjorkman, Andrea;Qvist, Per;Pan-Hammarstrom, Qiang
通讯作者：
Pan-Hammarstrom, Qiang