Characteristics of mutational signatures of unknown etiology.
Characteristics of mutational signatures of unknown etiology.
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作者：
Hu X;Xu Z;De S
虽然并非所有的体细胞突变都是癌症驱动因素，但它们的突变特征，即全基因组范围内的基因组改变模式，提供了对过去暴露于诱变剂，DNA损伤和修复过程的见解。体细胞突变模式的计算解卷积和专家策展泛癌症研究已经确定了许多与点突变、二核苷酸取代、插入和缺失以及重排相关的突变特征，并且已经确定了这些特征的子集的病因学。然而，近三分之一的突变签名的机制尚未被理解。具有确定病因的签名和那些迄今未知来源的签名似乎在链偏差、GC含量和核苷酸背景多样性方面存在一些差异。可能一些迄今为止“未知”的签名主要发生在基因区域之外。虽然核苷酸背景可能足以建立一些突变标签的病因学，但在其他情况下，额外的特征，例如更广泛的（epi）基因组背景，包括染色质、复制时间、持续合成能力和局部突变模式，可能有助于充分理解潜在的DNA损伤和修复过程。了解疾病的病因，并为癌症预防、风险管理和治疗决策提供了新的机会。
Although not all somatic mutations are cancer drivers, their mutational signatures, i.e. the patterns of genomic alterations at a genome-wide scale, provide insights into past exposure to mutagens, DNA damage and repair processes. Computational deconvolution of somatic mutation patterns and expert curation pan-cancer studies have identified a number of mutational signatures associated with point mutations, dinucleotide substitutions, insertions and deletions, and rearrangements, and have established etiologies for a subset of these signatures. However, the mechanisms underlying nearly one-third of all mutational signatures are not yet understood. The signatures with established etiology and those with hitherto unknown origin appear to have some differences in strand bias, GC content and nucleotide context diversity. It is possible that some of the hitherto ‘unknown’ signatures predominantly occur outside gene regions. While nucleotide contexts might be adequate to establish etiologies of some mutational signatures, in other cases additional features, such as broader (epi)genomic contexts, including chromatin, replication timing, processivity and local mutational patterns, may help fully understand the underlying DNA damage and repair processes. Nonetheless, remarkable progress in characterization of mutational signatures has provided fundamental insights into the biology of cancer, informed disease etiology and opened up new opportunities for cancer prevention, risk management, and therapeutic decision making.
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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：
7
作者：
Boot A;Huang MN;Ng AWT;Ho SC;Lim JQ;Kawakami Y;Chayama K;Teh BT;Nakagawa H;Rozen SG
通讯作者：
Rozen SG
影响因子：
12.3
作者：
Blokzijl F;Janssen R;van Boxtel R;Cuppen E
通讯作者：
Cuppen E
影响因子：
4
作者：
Alexandrov, Ludmil B.;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
寻找癌症中的驱动突变：阐明背景突变过程的作用
影响因子：
4.3
作者：
Brown, Anna-Leigh;Li, Minghui;Panchenko, Anna R.
通讯作者：
Panchenko, Anna R.