A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer.
A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer.
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DOI：
10.1038/ng.3934
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发表时间：
2017-10
期刊：
影响因子：
30.8
通讯作者：
Getz G
中科院分区：
文献类型：
--
作者：
Polak P;Kim J;Braunstein LZ;Karlic R;Haradhavala NJ;Tiao G;Rosebrock D;Livitz D;Kübler K;Mouw KW;Kamburov A;Maruvka YE;Leshchiner I;Lander ES;Golub TR;Zick A;Orthwein A;Lawrence MS;Batra RN;Caldas C;Haber DA;Laird PW;Shen H;Ellisen LW;D'Andrea AD;Chanock SJ;Foulkes WD;Getz G
BRCA 1/2的双等位基因失活与称为Signature 3的全基因组突变模式相关。通过分析约1，000个乳腺癌样本，我们证实了这种关联，并确定PALB 2中的种系无义和移码变体，而不是ATM或CHEK 2，也可以产生相同的签名。已知会损害同源重组（HR）的错义BRCA 1/2变体可通过该特征进行准确分类。最后，我们发现，启动子甲基化导致的RAD 51 C和BRCA 1的表观遗传沉默与Signature 3密切相关，并且在我们的数据集中，在非洲裔年轻患者的基底样乳腺癌中高度富集。
Biallelic inactivation of BRCA1/2 is associated with a pattern of genome-wide mutations known as Signature 3. By analyzing ~1,000 breast cancer samples, we confirmed this association and established that germline nonsense and frameshift variants in PALB2, but not ATM or CHEK2, can also give rise to the same signature. Missense BRCA1/2 variants known to impair homologous recombination (HR) were accurately classified by this signature. Finally, we show that epigenetic silencing of RAD51C and BRCA1 by promoter methylation are strongly associated with Signature 3 and, in our dataset, were highly enriched in basal-like breast cancers in young patients of African descent.
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影响因子：
19
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
通讯作者：
D'Andrea AD
影响因子：
4.8
作者：
Hashizume, R;Fukuda, M;Ohta, T
通讯作者：
Ohta, T
影响因子：
10.3
作者：
Esteller, M;Silva, JM;Herman, JG
通讯作者：
Herman, JG
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
14.9
作者：
Costello M;Pugh TJ;Fennell TJ;Stewart C;Lichtenstein L;Meldrim JC;Fostel JL;Friedrich DC;Perrin D;Dionne D;Kim S;Gabriel SB;Lander ES;Fisher S;Getz G
通讯作者：
Getz G