Pan-cancer analysis of bi-allelic alterations in homologous recombination DNA repair genes.
Pan-cancer analysis of bi-allelic alterations in homologous recombination DNA repair genes.
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DOI：
10.1038/s41467-017-00921-w
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发表时间：
2017-10-11
影响因子：
16.6
通讯作者：
Reis-Filho JS
中科院分区：
文献类型：
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作者：
Riaz N;Blecua P;Lim RS;Shen R;Higginson DS;Weinhold N;Norton L;Weigelt B;Powell SN;Reis-Filho JS
BRCA1基因和BRCA2基因参与同源重组(HR)DNA修复，是导致遗传性乳腺癌和卵巢癌(HBOC)综合征的胚系癌症易感基因。这些基因或HR途径其他成员的生殖系或体细胞变化，以及HR相关基因的单等位基因或双等位基因变化是否对其他癌症有表型影响，仍有待完全阐明。在这里，我们对癌症基因组图谱(TCGA)数据集进行泛癌分析，并观察到同源重组(HR)DNA修复相关基因的双等位致病改变在许多恶性肿瘤中普遍存在。这些双等位基因改变往往与HR缺乏症的基因组特征有关。此外，在卵巢癌、乳腺癌和前列腺癌中，双等位基因的改变是相互排斥的。这两个特性的结合有助于对影响DNA修复基因的未知重要性的变异进行重新分类，并可能有助于在临床上个性化HR定向治疗。同源重组(HR)DNA修复基因的胚系突变与乳腺癌和卵巢癌有关。在这里，作者表明，HR基因的互斥双等位基因失活存在于其他类型的癌症中，并与HR缺乏症的基因组特征有关，从而扩大了HR导向治疗的潜在用途。
BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair and are germ-line cancer pre-disposition genes that result in a syndrome of hereditary breast and ovarian cancer (HBOC). Whether germ-line or somatic alterations in these genes or other members of the HR pathway and if mono- or bi-allelic alterations of HR-related genes have a phenotypic impact on other cancers remains to be fully elucidated. Here, we perform a pan-cancer analysis of The Cancer Genome Atlas (TCGA) data set and observe that bi-allelic pathogenic alterations in homologous recombination (HR) DNA repair-related genes are prevalent across many malignancies. These bi-allelic alterations often associate with genomic features of HR deficiency. Further, in ovarian, breast and prostate cancers, bi-allelic alterations are mutually exclusive of each other. The combination of these two properties facilitates reclassification of variants of unknown significance affecting DNA repair genes, and may help personalize HR directed therapies in the clinic. Germline mutations in homologous recombination (HR) DNA repair genes are linked to breast and ovarian cancer. Here, the authors show that mutually exclusive bi-allelic inactivation of HR genes are present in other cancer types and associated with genomic features of HR deficiency, expanding the potential use of HR-directed therapies.
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影响因子：
9.8
作者：
Easton, Douglas F.;Deffenbaugh, Amie M.;Goldgar, David E.
通讯作者：
Goldgar, David E.
DOI：
10.1002/path.4890
发表时间：
2017-06
期刊：
The Journal of pathology
影响因子：
--
作者：
Mutter RW;Riaz N;Ng CK;Delsite R;Piscuoglio S;Edelweiss M;Martelotto LG;Sakr RA;King TA;Giri DD;Drobnjak M;Brogi E;Bindra R;Bernheim G;Lim RS;Blecua P;Desrichard A;Higginson D;Towers R;Jiang R;Lee W;Weigelt B;Reis-Filho JS;Powell SN
通讯作者：
Powell SN
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：
28.2
作者：
Birkbak NJ;Wang ZC;Kim JY;Eklund AC;Li Q;Tian R;Bowman-Colin C;Li Y;Greene-Colozzi A;Iglehart JD;Tung N;Ryan PD;Garber JE;Silver DP;Szallasi Z;Richardson AL
通讯作者：
Richardson AL
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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