Mitochondrial mutations drive prostate cancer aggression.
Mitochondrial mutations drive prostate cancer aggression.
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DOI：
10.1038/s41467-017-00377-y
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发表时间：
2017-09-22
影响因子：
16.6
通讯作者：
Boutros PC
中科院分区：
文献类型：
--
作者：
Hopkins JF;Sabelnykova VY;Weischenfeldt J;Simon R;Aguiar JA;Alkallas R;Heisler LE;Zhang J;Watson JD;Chua MLK;Fraser M;Favero F;Lawerenz C;Plass C;Sauter G;McPherson JD;van der Kwast T;Korbel J;Schlomm T;Bristow RG;Boutros PC
核突变是众所周知的驱动肿瘤发病率，侵略性和对治疗的反应。相比之下，母系遗传线粒体基因组中突变的频率和作用知之甚少。在这里，我们对384名局限性前列腺癌患者的线粒体基因组进行测序，并确定每位患者的线粒体单核苷酸变异（mtSNV）的中位数。这些mtSNV中的一些发生在复发性突变热点中，并与侵袭性疾病相关。年轻患者的mtSNV比老年患者少。我们证明了线粒体和核突变谱之间的密切联系，特定突变之间的共同发生。例如，某些控制区mtSNV与MYC癌基因的获得共同发生，并且这些突变与患者存活率共同相关。这些数据表明前列腺癌中线粒体突变频繁，并表明前列腺癌中细胞核和线粒体突变谱之间的相互作用。在前列腺癌中，突变在母系遗传的线粒体基因组中的作用尚不清楚。在这里，作者证明了前列腺癌中频繁的年龄依赖性线粒体突变。线粒体和核突变谱之间的紧密联系与临床攻击性相关。
Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer patients, and identify a median of one mitochondrial single-nucleotide variant (mtSNV) per patient. Some of these mtSNVs occur in recurrent mutational hotspots and associate with aggressive disease. Younger patients have fewer mtSNVs than those who diagnosed at an older age. We demonstrate strong links between mitochondrial and nuclear mutational profiles, with co-occurrence between specific mutations. For example, certain control region mtSNVs co-occur with gain of the MYC oncogene, and these mutations are jointly associated with patient survival. These data demonstrate frequent mitochondrial mutation in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer. In prostate cancer, the role of mutations in the maternally-inherited mitochondrial genome are not well known. Here, the authors demonstrate frequent, age-dependent mitochondrial mutation in prostate cancer. Strong links between mitochondrial and nuclear mutational profiles are associated with clinical aggressivity.
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影响因子：
4.5
作者：
Ding J;Sidore C;Butler TJ;Wing MK;Qian Y;Meirelles O;Busonero F;Tsoi LC;Maschio A;Angius A;Kang HM;Nagaraja R;Cucca F;Abecasis GR;Schlessinger D
通讯作者：
Schlessinger D
影响因子：
7.7
作者：
Ju YS;Alexandrov LB;Gerstung M;Martincorena I;Nik-Zainal S;Ramakrishna M;Davies HR;Papaemmanuil E;Gundem G;Shlien A;Bolli N;Behjati S;Tarpey PS;Nangalia J;Massie CE;Butler AP;Teague JW;Vassiliou GS;Green AR;Du MQ;Unnikrishnan A;Pimanda JE;Teh BT;Munshi N;Greaves M;Vyas P;El-Naggar AK;Santarius T;Collins VP;Grundy R;Taylor JA;Hayes DN;Malkin D;ICGC Breast Cancer Group;ICGC Chronic Myeloid Disorders Group;ICGC Prostate Cancer Group;Foster CS;Warren AY;Whitaker HC;Brewer D;Eeles R;Cooper C;Neal D;Visakorpi T;Isaacs WB;Bova GS;Flanagan AM;Futreal PA;Lynch AG;Chinnery PF;McDermott U;Stratton MR;Campbell PJ
通讯作者：
Campbell PJ
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
14.9
作者：
CORTOPASSI, GA;ARNHEIM, N
通讯作者：
ARNHEIM, N
影响因子：
9.8
作者：
Kloss-Brandstaetter, Anita;Schaefer, Georg;Kronenberg, Florian
通讯作者：
Kronenberg, Florian