Mutational signatures of ionizing radiation in second malignancies.
Mutational signatures of ionizing radiation in second malignancies.
复制标题
DOI：
10.1038/ncomms12605
复制
发表时间：
2016-09-12
影响因子：
16.6
通讯作者：
Campbell, Peter J.
中科院分区：
文献类型：
--
作者：
Behjati, Sam;Gundem, Gunes;Wedge, David C.;Roberts, Nicola D.;Tarpey, Patrick S.;Cooke, Susanna L.;Van Loo, Peter;Alexandrov, Ludmil B.;Ramakrishna, Manasa;Davies, Helen;Nik-Zainal, Serena;Hardy, Claire;Latimer, Calli;Raine, Keiran M.;Stebbings, Lucy;Menzies, Andy;Jones, David;Shepherd, Rebecca;Butler, Adam P.;Teague, Jon W.;Jorgensen, Mette;Khatri, Bhavisha;Pillay, Nischalan;Shlien, Adam;Futreal, P. Andrew;Badie, Christophe;McDermott, Ultan;Bova, G. Steven;Richardson, Andrea L.;Flanagan, Adrienne M.;Stratton, Michael R.;Campbell, Peter J.
电离辐射是一种强致癌物，通过DNA损伤诱发癌症。在体内暴露于电离辐射后，人体组织中产生的突变特征尚未被记录在案。在这里，我们在12种不同肿瘤类型的辐射相关的第二恶性肿瘤中寻找电离辐射的特征。与肿瘤类型无关的电离辐射暴露的两个体细胞突变特征。与319例辐射初始肿瘤相比，辐射相关肿瘤在全基因组范围内携带201个缺失，大小为1-100个碱基对，通常在连接处具有微同源性。与辐射初始肿瘤的缺失不同，这些缺失在整个基因组的密度上没有变化，也没有与序列背景、复制时间或染色质结构的相关性。此外，我们观察到辐射相关肿瘤中平衡反转的显著增加。小的缺失和反转都会产生驱动突变。因此，电离辐射产生独特的突变特征，解释了其致癌潜力。电离辐射可能导致无法修复的DNA损伤，从而导致癌症。在这里，作者确定了暴露于电离辐射的患者中产生的特定突变特征，并表明辐射诱导的肿瘤发生与更高的全基因组缺失率和平衡反转有关。
Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been documented. Here, we searched for signatures of ionizing radiation in 12 radiation-associated second malignancies of different tumour types. Two signatures of somatic mutation characterize ionizing radiation exposure irrespective of tumour type. Compared with 319 radiation-naive tumours, radiation-associated tumours carry a median extra 201 deletions genome-wide, sized 1–100 base pairs often with microhomology at the junction. Unlike deletions of radiation-naive tumours, these show no variation in density across the genome or correlation with sequence context, replication timing or chromatin structure. Furthermore, we observe a significant increase in balanced inversions in radiation-associated tumours. Both small deletions and inversions generate driver mutations. Thus, ionizing radiation generates distinctive mutational signatures that explain its carcinogenic potential. Ionizing radiation may induce irreparable DNA damage leading to cancer. Here, the authors identify a specific signature of mutations arising in patients exposed to ionizing radiation and suggest that radiation-induced tumorigenesis is associated with higher rates of genome-wide deletions and balanced inversions.
登录
查看更多内容
影响因子：
64.8
作者：
Nik-Zainal S;Davies H;Staaf J;Ramakrishna M;Glodzik D;Zou X;Martincorena I;Alexandrov LB;Martin S;Wedge DC;Van Loo P;Ju YS;Smid M;Brinkman AB;Morganella S;Aure MR;Lingjærde OC;Langerød A;Ringnér M;Ahn SM;Boyault S;Brock JE;Broeks A;Butler A;Desmedt C;Dirix L;Dronov S;Fatima A;Foekens JA;Gerstung M;Hooijer GK;Jang SJ;Jones DR;Kim HY;King TA;Krishnamurthy S;Lee HJ;Lee JY;Li Y;McLaren S;Menzies A;Mustonen V;O'Meara S;Pauporté I;Pivot X;Purdie CA;Raine K;Ramakrishnan K;Rodríguez-González FG;Romieu G;Sieuwerts AM;Simpson PT;Shepherd R;Stebbings L;Stefansson OA;Teague J;Tommasi S;Treilleux I;Van den Eynden GG;Vermeulen P;Vincent-Salomon A;Yates L;Caldas C;van't Veer L;Tutt A;Knappskog S;Tan BK;Jonkers J;Borg Å;Ueno NT;Sotiriou C;Viari A;Futreal PA;Campbell PJ;Span PN;Van Laere S;Lakhani SR;Eyfjord JE;Thompson AM;Birney E;Stunnenberg HG;van de Vijver MJ;Martens JW;Børresen-Dale AL;Richardson AL;Kong G;Thomas G;Stratton MR
通讯作者：
Stratton MR
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Adewoye, Adeolu B.;Lindsay, Sarah J.;Dubrova, Yuri E.;Hurles, Matthew E.
通讯作者：
Hurles, Matthew E.
DOI：
10.1016/s0027-5107(96)00209-6
发表时间：
1996-11-11
影响因子：
2.3
作者：
Natarajan, AT;Boei, JJWA;Balajee, AS
通讯作者：
Balajee, AS
影响因子：
64.5
作者：
Nik-Zainal S;Van Loo P;Wedge DC;Alexandrov LB;Greenman CD;Lau KW;Raine K;Jones D;Marshall J;Ramakrishna M;Shlien A;Cooke SL;Hinton J;Menzies A;Stebbings LA;Leroy C;Jia M;Rance R;Mudie LJ;Gamble SJ;Stephens PJ;McLaren S;Tarpey PS;Papaemmanuil E;Davies HR;Varela I;McBride DJ;Bignell GR;Leung K;Butler AP;Teague JW;Martin S;Jönsson G;Mariani O;Boyault S;Miron P;Fatima A;Langerød A;Aparicio SA;Tutt A;Sieuwerts AM;Borg Å;Thomas G;Salomon AV;Richardson AL;Børresen-Dale AL;Futreal PA;Stratton MR;Campbell PJ;Breast Cancer Working Group of the International Cancer Genome Consortium
通讯作者：
Breast Cancer Working Group of the International Cancer Genome Consortium