Deep Genetic Connection Between Cancer and Developmental Disorders.
Deep Genetic Connection Between Cancer and Developmental Disorders.
复制标题
DOI：
10.1002/humu.23040
复制
发表时间：
2016-10
期刊：
影响因子：
3.9
通讯作者：
Shen, Yufeng
中科院分区：
文献类型：
--
作者：
Qi, Hongjian;Dong, Chengliang;Chung, Wendy K.;Wang, Kai;Shen, Yufeng
癌症和发育障碍（DD）共享失调的细胞过程，例如增殖和分化。有一些众所周知的基因与癌症和DD有关。在这项研究中，我们的目标是使用公开的数据来量化这种遗传联系。我们发现，在DD患者中，生殖系损伤性从头变异比非驱动基因更富含癌症驱动基因。我们估计，癌症驱动基因约占DD风险基因的三分之一。此外，从头可能基因破坏（LGD）变体在肿瘤抑制因子中更富集，约40%的涉及的从头破坏性错义变体位于癌症体细胞突变热点，表明许多基因在癌症和DD中具有相似的作用模式。我们的研究结果表明，我们可以将肿瘤视为天然实验室，用于评估适用于种系变异的突变的有害影响，并鉴定DD中的致病基因和变异。
Cancer and developmental disorders (DD) share dysregulated cellular processes such as proliferation and differentiation. There are well-known genes implicated in both in cancer and DD. In this study, we aim to quantify this genetic connection using publicly available data. We found that among DD patients, germline damaging de novo variants are more enriched in cancer driver genes than non-drivers. We estimate that cancer driver genes comprise about a third of DD risk genes. Additionally, de novo likely-gene-disrupting (LGD) variants are more enriched in tumor suppressors, and about 40% of implicated de novo damaging missense variants are located in cancer somatic mutation hotspots, indicating that many genes have a similar mode of action in cancer and DD. Our results suggest that we can view tumors as natural laboratories for assessing the deleterious effects of mutations that are applicable to germline variants and identification of causal genes and variants in DD.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
3.7
作者：
Darbro BW;Singh R;Zimmerman MB;Mahajan VB;Bassuk AG
通讯作者：
Bassuk AG
影响因子：
30.8
作者：
De Keersmaecker K;Atak ZK;Li N;Vicente C;Patchett S;Girardi T;Gianfelici V;Geerdens E;Clappier E;Porcu M;Lahortiga I;Lucà R;Yan J;Hulselmans G;Vranckx H;Vandepoel R;Sweron B;Jacobs K;Mentens N;Wlodarska I;Cauwelier B;Cloos J;Soulier J;Uyttebroeck A;Bagni C;Hassan BA;Vandenberghe P;Johnson AW;Aerts S;Cools J
通讯作者：
Cools J