The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer.
The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer.
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DOI：
10.3390/jcm12020623
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发表时间：
2023-01-12
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
--
作者：
具有错配修复缺陷（MMR-d）的前列腺癌具有侵袭性的临床和组织学特征，并且它们对免疫治疗有潜在的响应。然而，它的稀有性阻碍了对潜在生物学的分析。在这里，我们从GENIE和TCGA数据库中收集了2664例原发性前列腺肿瘤和1409例转移性前列腺肿瘤的基因组数据。在这些肿瘤中，共确定了69例（2.59%）原发性和60例（4.26%）转移性MMR-d肿瘤。34个候选基因（包括KMT 2D（46.4%）、ZFHX 3（33.3%）、JAK 1（31.9%）和RNF 43（27.5%））和16个候选基因（包括KMT 2D（33.3%）和JAK 1（28.3%））的SNV频率在MMR-d原发性肿瘤和MMR-d转移性肿瘤中分别较高。原发性MMR-d肿瘤的肿瘤突变负荷（TMB）较高。EPCAM和EPAS 1的纯合缺失在MMR-d原发性肿瘤中富集，而EPCAM缺失在转移性MMR-d肿瘤中富集。对于基因组重排事件，TMPRSS 2-ETS融合在原发性MMR-d肿瘤中不太常见。我们的研究表明MMR-d前列腺癌具有独特的基因组特征。这些可能在为治疗该前列腺癌患者子集提供治疗靶点方面发挥重要作用。
Prostate cancers with mismatch repair deficiency (MMR-d) have aggressive clinical and histological features, and they are potentially responsive to immunotherapy. However, its rarity prevents the analysis of the underlying biology. Here, we collected the genomic data of 2664 primary prostate tumors and 1409 metastatic prostate tumors from the GENIE and TCGA databases. A total of 69 (2.59%) primary and 60 (4.26%) metastatic MMR-d tumors were identified among these tumors. Single nucleotide variant (SNV) frequencies of 34 candidate genes (including KMT2D (46.4%), ZFHX3 (33.3%), JAK1 (31.9%), and RNF43 (27.5%)) and 16 candidate genes (including KMT2D (33.3%) and JAK1 (28.3%)) were higher in MMR-d primary tumors and MMR-d metastatic tumors, respectively. The tumor mutation burden (TMB) was higher in primary MMR-d tumors. Homozygous deletions of EPCAM and EPAS1 were enriched in MMR-d primary tumors, while EPCAM deletions were enriched in metastatic MMR-d tumors. For genomic rearrangement events, TMPRSS2-ETS fusions were less frequent in primary MMR-d tumors. Our study indicates MMR-d prostate cancers have unique genomic features. These may play an important role in providing therapeutic targets for the treatment of this subset of prostate cancer patients.
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癌症驱动器MLL2的突变导致转录应力和基因组不稳定性。
影响因子：
10.5
作者：
Kantidakis T;Saponaro M;Mitter R;Horswell S;Kranz A;Boeing S;Aygün O;Kelly GP;Matthews N;Stewart A;Stewart AF;Svejstrup JQ
通讯作者：
Svejstrup JQ
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
DOI：
10.1093/database/baq020
发表时间：
2010-08-05
期刊：
Database : the journal of biological databases and curation
影响因子：
--
作者：
Safran M;Dalah I;Alexander J;Rosen N;Iny Stein T;Shmoish M;Nativ N;Bahir I;Doniger T;Krug H;Sirota-Madi A;Olender T;Golan Y;Stelzer G;Harel A;Lancet D
通讯作者：
Lancet D
DOI：
10.1016/s1470-2045(21)00522-2
发表时间：
2021-11
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Bancroft EK;Page EC;Brook MN;Thomas S;Taylor N;Pope J;McHugh J;Jones AB;Karlsson Q;Merson S;Ong KR;Hoffman J;Huber C;Maehle L;Grindedal EM;Stormorken A;Evans DG;Rothwell J;Lalloo F;Brady AF;Bartlett M;Snape K;Hanson H;James P;McKinley J;Mascarenhas L;Syngal S;Ukaegbu C;Side L;Thomas T;Barwell J;Teixeira MR;Izatt L;Suri M;Macrae FA;Poplawski N;Chen-Shtoyerman R;Ahmed M;Musgrave H;Nicolai N;Greenhalgh L;Brewer C;Pachter N;Spigelman AD;Azzabi A;Helfand BT;Halliday D;Buys S;Ramon Y Cajal T;Donaldson A;Cooney KA;Harris M;McGrath J;Davidson R;Taylor A;Cooke P;Myhill K;Hogben M;Aaronson NK;Ardern-Jones A;Bangma CH;Castro E;Dearnaley D;Dias A;Dudderidge T;Eccles DM;Green K;Eyfjord J;Falconer A;Foster CS;Gronberg H;Hamdy FC;Johannsson O;Khoo V;Lilja H;Lindeman GJ;Lubinski J;Axcrona K;Mikropoulos C;Mitra AV;Moynihan C;Ni Raghallaigh H;Rennert G;Collier R;IMPACT Study Collaborators;Offman J;Kote-Jarai Z;Eeles RA
通讯作者：
Eeles RA
影响因子：
30.8
作者：
King, Jennifer C.;Xu, Jin;Wongvipat, John;Hieronymus, Haley;Carver, Brett S.;Leung, David H.;Taylor, Barry S.;Sander, Chris;Cardiff, Robert D.;Couto, Suzana S.;Gerald, William L.;Sawyers, Charles L.
通讯作者：
Sawyers, Charles L.