Inferring early genetic progression in cancers with unobtainable premalignant disease.
Inferring early genetic progression in cancers with unobtainable premalignant disease.
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DOI：
10.1038/s43018-023-00533-y
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发表时间：
2023-04
期刊：
影响因子：
22.7
通讯作者：
Rocco, James W.
中科院分区：
文献类型：
--
作者：
Leshchiner, Ignaty;Mroz, Edmund A.;Cha, Justin;Rosebrock, Daniel;Spiro, Oliver;Bonilla-Velez, Juliana;Faquin, William C.;Lefranc-Torres, Armida;Lin, Derrick T.;Michaud, William A.;Getz, Gad;Rocco, James W.
癌前组织的分析已经确定了在几种癌症类型中导致侵袭性肿瘤的体细胞事件的典型顺序。对于其他癌症，癌前组织是无法获得的，使遗传进展未知。在这里，我们展示了如何从原发性肿瘤的外显子组测序中推断进展。我们的计算方法，PhylogicNDT，概括了以前的实验确定的人乳头瘤病毒阴性（HPV-）的头颈部鳞状细胞癌（HNSCC）的遗传进展。然后，我们评估了HPV+ HNSCC，它缺乏癌前组织，并发现了其以前未知的进展，确定了早期驱动因素。我们基于时钟样突变特征将驱动突变和HPV整合的相对时间估计转换为诊断前几年。我们将肿瘤内遗传异质性增加和总生存期缩短与非整倍体转变的时间相关联。我们的方法可以用无法获得的癌前组织建立以前未知的癌症早期遗传进展，支持早期检测，拦截和预测的实验模型和方法的发展。Getz及其同事展示了一种计算方法，以HPV阴性和HPV阳性头颈部鳞状细胞癌为例，估计基因组驱动因素在没有癌前病变的癌症类型的早期肿瘤进展中的时间。
Analysis of premalignant tissue has identified the typical order of somatic events leading to invasive tumors in several cancer types. For other cancers, premalignant tissue is unobtainable, leaving genetic progression unknown. Here, we demonstrate how to infer progression from exome sequencing of primary tumors. Our computational method, PhylogicNDT, recapitulated the previous experimentally determined genetic progression of human papillomavirus-negative (HPV–) head and neck squamous cell carcinoma (HNSCC). We then evaluated HPV+ HNSCC, which lacks premalignant tissue, and uncovered its previously unknown progression, identifying early drivers. We converted relative timing estimates of driver mutations and HPV integration to years before diagnosis based on a clock-like mutational signature. We associated the timing of transitions to aneuploidy with increased intratumor genetic heterogeneity and shorter overall survival. Our approach can establish previously unknown early genetic progression of cancers with unobtainable premalignant tissue, supporting development of experimental models and methods for early detection, interception and prognostication. Getz and colleagues demonstrate a computational approach to estimate the timing of genomic drivers in early tumor progression from cancer types that do not have premalignant disease, using HPV-negative and HPV-positive head and neck squamous cell carcinoma as examples.
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DOI：
10.3233/cbm-2011-0166
发表时间：
2010
期刊：
Cancer biomarkers : section A of Disease markers
影响因子：
--
作者：
Gazdar AF;Brambilla E
通讯作者：
Brambilla E
影响因子：
7
作者：
Gillison, Maura L.;Akagi, Keiko;Symer, David E.
通讯作者：
Symer, David E.
影响因子：
7.3
作者：
Ghosh, Amlan;Ghosh, Susmita;Panda, Chinmay K.
通讯作者：
Panda, Chinmay K.
DOI：
10.1158/1078-0432.ccr-11-1944
发表时间：
2011-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bhattacharya A;Roy R;Snijders AM;Hamilton G;Paquette J;Tokuyasu T;Bengtsson H;Jordan RC;Olshen AB;Pinkel D;Schmidt BL;Albertson DG
通讯作者：
Albertson DG
影响因子：
45.3
作者：
Chaturvedi, Anil K.;Engels, Eric A.;Gillison, Maura L.
通讯作者：
Gillison, Maura L.