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肿瘤和循环游离DNA甲基化可识别临床相关的小细胞肺癌亚型
作者:小柯机器人 发布时间:2024/1/27 22:47:03

美国德克萨斯大学John V. Heymach等研究人员合作发现,肿瘤和循环游离DNA甲基化可识别临床相关的小细胞肺癌亚型。该项研究成果于2024年1月25日在线发表在《癌细胞》杂志上。

鉴于已知的小细胞肺癌(SCLC)关键转录程序的表观遗传调控,研究人员假设可以在SCLC患者的肿瘤或血液中检测到亚型特异的DNA甲基化模式。通过对两个队列共179例SCLC患者进行全基因组还原亚硫酸氢盐测序(RRBS),并采用机器学习方法,研究人员报告了一种高度准确的基于DNA甲基化的分类器(SCLC-DMC),它可以区分SCLC亚型。研究人员进一步调整了循环游离DNA(cfDNA)分类器,以便从血浆中对SCLC进行亚型分类。

通过使用cfDNA分类器(cfDMC),研究人员证明了SCLC表型在疾病进展过程中会发生演变,从而突出了在临床治疗过程中对SCLC进行纵向追踪的必要性。这些数据证明,肿瘤和cfDNA甲基化可用于识别SCLC亚型,并可指导SCLC的精准治疗。

研究人员表示,SCLC是一种侵袭性恶性肿瘤,由不同的转录亚型组成,但在临床上进行亚型鉴定仍具有挑战性,特别是由于组织可用性有限。

附:英文原文

Title: Tumor- and circulating-free DNA methylation identifies clinically relevant small cell lung cancer subtypes

Author: Simon Heeke, Carl M. Gay, Marcos R. Estecio, Hai Tran, Benjamin B. Morris, Bingnan Zhang, Ximing Tang, Maria Gabriela Raso, Pedro Rocha, Siqi Lai, Edurne Arriola, Paul Hofman, Veronique Hofman, Prasad Kopparapu, Christine M. Lovly, Kyle Concannon, Luana Guimaraes De Sousa, Whitney Elisabeth Lewis, Kimie Kondo, Xin Hu, Azusa Tanimoto, Natalie I. Vokes, Monique B. Nilsson, Allison Stewart, Maarten Jansen, Ildikó Horváth, Mina Gaga, Vasileios Panagoulias, Yael Raviv, Danny Frumkin, Adam Wasserstrom, Aharona Shuali, Catherine A. Schnabel, Yuanxin Xi, Lixia Diao, Qi Wang, Jianjun Zhang, Peter Van Loo, Jing Wang, Ignacio I. Wistuba, Lauren A. Byers, John V. Heymach

Issue&Volume: 2024-01-25

Abstract: Small cell lung cancer (SCLC) is an aggressive malignancy composed of distinct transcriptional subtypes, but implementing subtyping in the clinic has remained challenging, particularly due to limited tissue availability. Given the known epigenetic regulation of critical SCLC transcriptional programs, we hypothesized that subtype-specific patterns of DNA methylation could be detected in tumor or blood from SCLC patients. Using genomic-wide reduced-representation bisulfite sequencing (RRBS) in two cohorts totaling 179 SCLC patients and using machine learning approaches, we report a highly accurate DNA methylation-based classifier (SCLC-DMC) that can distinguish SCLC subtypes. We further adjust the classifier for circulating-free DNA (cfDNA) to subtype SCLC from plasma. Using the cfDNA classifier (cfDMC), we demonstrate that SCLC phenotypes can evolve during disease progression, highlighting the need for longitudinal tracking of SCLC during clinical treatment. These data establish that tumor and cfDNA methylation can be used to identify SCLC subtypes and might guide precision SCLC therapy.

DOI: 10.1016/j.ccell.2024.01.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(24)00006-0

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:38.585
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx