Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.
Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.
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DOI：
10.1038/s41467-018-06616-0
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发表时间：
2018-10-16
影响因子：
16.6
通讯作者：
Barretina J
中科院分区：
文献类型：
--
作者：
Pitt JJ;Riester M;Zheng Y;Yoshimatsu TF;Sanni A;Oluwasola O;Veloso A;Labrot E;Wang S;Odetunde A;Ademola A;Okedere B;Mahan S;Leary R;Macomber M;Ajani M;Johnson RS;Fitzgerald D;Grundstad AJ;Tuteja JH;Khramtsova G;Zhang J;Sveen E;Hwang B;Clayton W;Nkwodimmah C;Famooto B;Obasi E;Aderoju V;Oludara M;Omodele F;Akinyele O;Adeoye A;Ogundiran T;Babalola C;MacIsaac K;Popoola A;Morrissey MP;Chen LS;Wang J;Olopade CO;Falusi AG;Winckler W;Haase K;Van Loo P;Obafunwa J;Papoutsakis D;Ojengbede O;Weber B;Ibrahim N;White KP;Huo D;Olopade OI;Barretina J
乳腺癌死亡率的种族/民族差异继续扩大，但基因组研究很少询问不同人群的乳腺癌。通过基因组、外显子组和RNA测序，我们研究了来自尼日利亚的194名患者和来自癌症基因组图谱（TCGA）的1037名患者的乳腺癌分子特征。与TCGA的黑人和白人相比，尼日利亚人的HR + /HER2−肿瘤的特点是同源重组缺陷特征增加，TP53突变普遍存在，结构变异更大，表明具有侵袭性生物学。无论亚型如何，GATA3突变在尼日利亚人中也更为常见。较高比例的apobecc介导的替换与PIK3CA和CDH1突变密切相关，这在尼日利亚人和黑人中代表性不足。PLK2、KDM6A和B2M也被确定为乳腺癌中先前未报道的显著突变基因。该数据集为结果差异的潜在分子机制提供了新的见解，并为在服务不足的人群中部署精确治疗奠定了基础。由于缺乏对不同人群的基因组研究，种族和族裔对乳腺癌死亡率影响的研究受到阻碍。在这里，作者对尼日利亚的194例乳腺癌进行了基因组调查，揭示了可以解释非洲土著人口中乳腺癌高死亡率的分子特征。
Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 − tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation—indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations. Research on racial and ethnic influence on breast cancer mortality is stymied by a lack of genomic studies in diverse populations. Here, the authors genomically interrogate 194 Nigerian breast cancers, unveiling molecular features that could explain the high mortality rate from breast cancer in an indigenous African population.
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影响因子：
50.3
作者：
Berger AC;Korkut A;Kanchi RS;Hegde AM;Lenoir W;Liu W;Liu Y;Fan H;Shen H;Ravikumar V;Rao A;Schultz A;Li X;Sumazin P;Williams C;Mestdagh P;Gunaratne PH;Yau C;Bowlby R;Robertson AG;Tiezzi DG;Wang C;Cherniack AD;Godwin AK;Kuderer NM;Rader JS;Zuna RE;Sood AK;Lazar AJ;Ojesina AI;Adebamowo C;Adebamowo SN;Baggerly KA;Chen TW;Chiu HS;Lefever S;Liu L;MacKenzie K;Orsulic S;Roszik J;Shelley CS;Song Q;Vellano CP;Wentzensen N;Cancer Genome Atlas Research Network;Weinstein JN;Mills GB;Levine DA;Akbani R
通讯作者：
Akbani R
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.8
作者：
Huo, D.;Adebamowo, C. A.;Ogundiran, T. O.;Akang, E. E.;Campbell, O.;Adenipekun, A.;Cummings, S.;Fackenthal, J.;Ademuyiwa, F.;Ahsan, H.;Olopade, O. I.
通讯作者：
Olopade, O. I.
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
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