DNArCdb: A database of cancer biomarkers in DNA repair genes that includes variants related to multiple cancer phenotypes.
DNArCdb: A database of cancer biomarkers in DNA repair genes that includes variants related to multiple cancer phenotypes.
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DOI：
10.1016/j.dnarep.2018.07.010
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发表时间：
2018-10
期刊：
影响因子：
3.8
通讯作者：
Cisneros GA
中科院分区：
文献类型：
--
作者：
Silvestrov P;Maier SJ;Fang M;Cisneros GA
发挥作用的DNA修复能力对于生物体确保生物信息的保存和正确传播至关重要。DNA修复途径的中断会导致DNA突变的积累，这可能会导致癌症等复杂疾病的发生。癌症相关生物标志物的发现和表征可能使早期诊断和靶向治疗成为可能，这将显著提高癌症患者的存活率。为此，我们应用了一种假设驱动的生物信息学方法来识别与25种不同DNA修复酶相关的生物标记物，并结合对新发现的与癌症表型相关的SNPs的六个精选错义突变的结构分析。我们对8个不同的癌症数据库的搜索发现了43个错义SNPs，这些SNPs在统计学上至少与一种表型显著相关。此外，这些错义SNP中有9个与两种或两种以上癌症有统计学意义的关联。此外，我们还用经典分子动力学方法研究了rs10018786对POLN的影响(导致M310L POLν变异)和rs3218784对POLI的影响(导致I236M POLι)。我们的结果表明，与它们各自的野生型蛋白相比，这两个与癌症相关的变体都会导致显著的结构和动态变化。
Functioning DNA repair capabilities are vital for organisms to ensure that the biological information is preserved and correctly propagated. Disruptions in DNA repair pathways can result in the accumulation of DNA mutations, which may lead to onset of complex disease such as cancer. The discovery and characterization of cancer-related biomarkers may allow early diagnosis and targeted treatment, which could significantly contribute to the survival rates of cancer patients. To this end, we have applied a hypothesis driven bioinformatics approach to identify biomarkers related to 25 different DNA repair enzymes, in combination with structural analysis of six selected missense mutations of newly discovered SNPs that are associated with cancer phenotypes. Our search on 8 distinct cancer databases uncovered 43 missense SNPs that statistically significantly associated at least one phenotype. Moreover, nine of these missense SNPs are statistically significantly associated with two or more cancers. In addition, we have performed classical molecular dynamics to characterize the impact of rs10018786 on POLN, which results in the M310L Pol ν variant, and rs3218784 on POLI, which results in the I236M Polι. Our results suggest that both of these cancer-associated variants result in noticeable structural and dynamical changes compared with their respective wild-type proteins.
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影响因子：
14.8
作者：
Clarke, Geraldine M.;Anderson, Carl A.;Pettersson, Fredrik H.;Cardon, Lon R.;Morris, Andrew P.;Zondervan, Krina T.
通讯作者：
Zondervan, Krina T.
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：
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影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG