Ultra-sensitive sequencing for cancer detection reveals progressive clonal selection in normal tissue over a century of human lifespan
Ultra-sensitive sequencing for cancer detection reveals progressive clonal selection in normal tissue over a century of human lifespan
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用于癌症检测的超灵敏测序揭示了人类一个世纪以来正常组织中的渐进克隆选择
DOI：
10.1101/457291
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
R. Risques
中科院分区：
文献类型：
--
作者：
J. Salk;Kaitlyn J. Loubet;E. Maritschnegg;C. Valentine;L. Williams;R. Horvat;A. Vanderstichele;D. Nachmanson;Kathryn T. Baker;M. Emond;Emily Loter;T. Soussi;L. Loeb;R. Zeillinger;P. Speiser;R. Risques
高精度的新一代DNA测序通过能够识别微创体液样本中的突变癌症分子，有望改变早期癌症检测的范式。我们展示了80%的敏感性卵巢癌检测使用超准确的双重测序，以确定子宫灌洗液中的TP53突变。然而，除了肿瘤DNA，我们还在几乎所有患有和不患有癌症的妇女的冲洗液中检测到低频率的TP53突变。这些突变随年龄增长而增加，并具有在人类肿瘤中常见的克隆性TP53突变的选择特征。我们发现，从新生儿到百岁老人的多种健康组织中都存在低频率的TP53突变，并且随着年龄的增长，各种组织类型的丰度和致病性逐渐增加。我们的结果表明，亚克隆癌症的进化过程是正常人类衰老过程中普遍存在的一部分，在高灵敏度的临床癌症诊断中，必须非常小心地区分肿瘤起源的突变和与年龄相关的突变。
High accuracy next-generation DNA sequencing promises a paradigm shift in early cancer detection by enabling the identification of mutant cancer molecules in minimally-invasive body fluid samples. We demonstrate 80% sensitivity for ovarian cancer detection using ultra-accurate Duplex Sequencing to identify TP53 mutations in uterine lavage. However, in addition to tumor DNA, we also detect low frequency TP53 mutations in nearly all lavages from women with and without cancer. These mutations increase with age and share the selection traits of clonal TP53 mutations commonly found in human tumors. We show that low frequency TP53 mutations exist in multiple healthy tissues, from newborn to centenarian, and progressively increase in abundance and pathogenicity with older age across tissue types. Our results illustrate that subclonal cancer evolutionary processes are a ubiquitous part of normal human aging and great care must be taken to distinguish tumor-derived, from age-associated mutations in high sensitivity clinical cancer diagnostics.
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
158.5
作者：
Shain, A. Hunter;Yeh, Iwei;Bastian, Boris C.
通讯作者：
Bastian, Boris C.
DOI：
10.1056/nejmoa1408617
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Jaiswal S;Fontanillas P;Flannick J;Manning A;Grauman PV;Mar BG;Lindsley RC;Mermel CH;Burtt N;Chavez A;Higgins JM;Moltchanov V;Kuo FC;Kluk MJ;Henderson B;Kinnunen L;Koistinen HA;Ladenvall C;Getz G;Correa A;Banahan BF;Gabriel S;Kathiresan S;Stringham HM;McCarthy MI;Boehnke M;Tuomilehto J;Haiman C;Groop L;Atzmon G;Wilson JG;Neuberg D;Altshuler D;Ebert BL
通讯作者：
Ebert BL