한빛사논문
- 조회619
Ignaty Leshchiner 1,11, Edmund A. Mroz 2,3,11, Justin Cha 1,11, Daniel Rosebrock 1, Oliver Spiro 1, Juliana Bonilla-Velez 4, William C. Faquin 5,6, Armida Lefranc-Torres 4, Derrick T. Lin 4, William A. Michaud 7, Gad Getz 1,6,8,9,12 & James W. Rocco 2,3,10,12
1Broad Institute of MIT and Harvard, Cambridge, MA, USA.
2Department of Otolaryngology—Head and Neck Surgery, The Ohio State University WexnerMedical Center, Columbus, OH, USA.
3The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, USA.
4Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA.
5Department of Pathology, Massachusetts Eye and Ear, Boston, MA, USA.
6Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
7Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
8Cancer Center, Massachusetts General Hospital, Boston, MA, USA.
9Harvard Medical School, Boston, MA, USA.
10The Ohio State University Comprehensive Cancer Center—James, The Ohio State University, Columbus, OH, USA.
11These authors contributed equally: Ignaty Leshchiner, Edmund A. Mroz, Justin Cha.
12These authors jointly supervised this work: Gad Getz, James W. Rocco.
Abstract
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.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-07-19)
- 국외 연구진
- 생명과학 > 유전학
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