Patterns and processes of somatic mutations in nine major cancers.
Patterns and processes of somatic mutations in nine major cancers.
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DOI：
10.1186/1755-8794-7-11
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发表时间：
2014-02-19
影响因子：
2.7
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Jia P;Pao W;Zhao Z
癌症基因组含有数百至数千个体细胞非同义突变。DNA损伤和DNA修复系统的缺陷是导致体细胞突变的两种主要力量，使癌症基因组具有特定的体细胞突变模式。最近，几项泛癌症基因组研究揭示了多种癌症类型的20多个突变特征。然而，详细的癌症类型特异性突变特征及其在（内）和（间）癌症类型内的不同特征仍然在很大程度上未被探索。我们采用矩阵分解算法，即非负矩阵分解，调查了9种主要人类癌症的体细胞突变，共涉及~2100个基因组。我们的研究结果揭示了每种癌症中3-5个独立的突变特征，这意味着每种癌症基因组可能存在3-5个主要突变过程。诱变剂暴露（烟草和阳光）和DNA修复系统（APOBEC家族，POLE和MLH 1）的变化被发现是诱变力，每一个都标志着基因组具有明显的突变特征。我们研究了几种标记的特征及其在癌症内和癌症间的组合模式。一方面，我们发现即使在相同的癌症类型中，每个标签也可以以不同的影响程度影响癌症基因组，并且标签特异性负荷反映了癌症内的异质性（例如，肺癌吸烟者和从不吸烟者的吸烟相关特征）。另一方面，癌症间异质性的特征在于突变特征的组合模式，其中没有癌症共享相同的特征谱，即使在两种肺癌亚型（肺腺癌和鳞状细胞肺癌）之间也是如此。我们的工作提供了九种主要癌症中每种癌症的突变特征的详细概述，并强调突变特征谱代表了每种癌症。
Cancer genomes harbor hundreds to thousands of somatic nonsynonymous mutations. DNA damage and deficiency of DNA repair systems are two major forces to cause somatic mutations, marking cancer genomes with specific somatic mutation patterns. Recently, several pan-cancer genome studies revealed more than 20 mutation signatures across multiple cancer types. However, detailed cancer-type specific mutation signatures and their different features within (intra-) and between (inter-) cancer types remain largely unexplored. We employed a matrix decomposition algorithm, namely Non-negative Matrix Factorization, to survey the somatic mutations in nine major human cancers, involving a total of ~2100 genomes. Our results revealed 3-5 independent mutational signatures in each cancer, implying that a range of 3-5 predominant mutational processes likely underlie each cancer genome. Both mutagen exposure (tobacco and sun) and changes in DNA repair systems (APOBEC family, POLE, and MLH1) were found as mutagenesis forces, each of which marks the genome with an evident mutational signature. We studied the features of several signatures and their combinatory patterns within and across cancers. On one hand, we found each signature may influence a cancer genome with different influential magnitudes even in the same cancer type and the signature-specific load reflects intra-cancer heterogeneity (e.g., the smoking-related signature in lung cancer smokers and never smokers). On the other hand, inter-cancer heterogeneity is characterized by combinatory patterns of mutational signatures, where no cancers share the same signature profile, even between two lung cancer subtypes (lung adenocarcinoma and squamous cell lung cancer). Our work provides a detailed overview of the mutational characteristics in each of nine major cancers and highlights that the mutational signature profile is representative of each cancer.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Burns, Michael B.;Temiz, Nuri A.;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.3
作者：
Bai H;Rolfe MD;Jia W;Coakley S;Poole RK;Green J;Holcombe M
通讯作者：
Holcombe M
DOI：
10.1126/science.1198056
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Li M;Zhang X;Jones S;Leary RJ;Lin JC;Boca SM;Carter H;Samayoa J;Bettegowda C;Gallia GL;Jallo GI;Binder ZA;Nikolsky Y;Hartigan J;Smith DR;Gerhard DS;Fults DW;VandenBerg S;Berger MS;Marie SK;Shinjo SM;Clara C;Phillips PC;Minturn JE;Biegel JA;Judkins AR;Resnick AC;Storm PB;Curran T;He Y;Rasheed BA;Friedman HS;Keir ST;McLendon R;Northcott PA;Taylor MD;Burger PC;Riggins GJ;Karchin R;Parmigiani G;Bigner DD;Yan H;Papadopoulos N;Vogelstein B;Kinzler KW;Velculescu VE
通讯作者：
Velculescu VE