Divergent genomic evolution in astrocytomas and oligodendrogliomas.
一项发表于《自然》的研究利用全基因组和全外显子组测序，对胶质瘤纵向分析联盟收集的183例IDH突变型胶质瘤患者的纵向肿瘤标本进行了分析，多数原发手术样本组织学分级为2级（星形细胞瘤73%，少突胶质细胞瘤93%）。研究验证了肿瘤进展的已知基因组标志物，包括超突变及CDKN2A/B纯合缺失，并发现星形细胞瘤与少突胶质细胞瘤的演化轨迹存在差异：复发性少突胶质细胞瘤新获得PI3K和NOTCH1突变，与肿瘤突变负荷增加相关；复发性星形细胞瘤则获得局灶性癌基因扩增和CDKN2A/B纯合缺失，与染色体失衡增加相关，并伴随染色体碎裂和全基因组加倍等标志。两类肿瘤均出现获得性改变与全基因组变化的趋同及患者预后恶化，提示治疗难治性克隆被选择。替莫唑胺治疗与SBS11和SBS119突变特征相关，放疗相关ID8特征仅在星形细胞瘤中增加。研究表明，两类肿瘤基因组以不同方式适应肿瘤进展和治疗的选择压力。
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完整作者
Tamrin Chowdhury、C Mircea S Tesileanu、Emre Kocakavuk、Kevin C Johnson、Joo Ho Lee、Zeynep Erson-Omay、Chaewon Heo、Kenneth Aldape、Samirkumar B Amin、Kevin J Anderson、David M Ashley、Floris P Barthel、Jill S Barnholtz-Sloan、Daniel J Brat、Andrew R Brodbelt、Ana Valeria Castro、Elizabeth B Claus、Jennifer M Connelly、Joseph F Costello、Indrani Datta、Carol Elliott、Gaetano Finocchiaro、Pim J French、Hui K Gan、Luciano Garofano、Padmaja L Ghospurkar、Anna Golebiewska、Pranav S Gundla、Beth Hermes、Chibo Hong、Youri Hoogstrate、Craig Horbinski、Jason T Huse、Antonio Iavarone、Cihat Karadag、Mustafa Khasraw、Mathilde C M Kouwenhoven、Peter S LaViolette、Kay Li、Allison Lowman、Katy McCortney、Hyo-Eun Moon、Nader Sanai、MacLean P Nasrallah、H K Ng、D Ryan Ormond、Bethany Kwan、Marta Padovan、Sun Ha Paek、Laila M Poisson、Sushant Puri、Erica Shen、Shwetal Mehta、Andrew E Sloan、Wies R Vallentgoed、Erwin G Van Meir、Rachael Vaubel、Taylor E Wade、Annemiek M E Walenkamp、Colin Watts、Tobias Weiss、Michael Weller、Pieter Wesseling、Kerryn Westcott、Bart A Westerman、Gordon Y Ye、W K Alfred Yung、GLASS Consortium、Frederick S Varn、Roel G W Verhaak
作者机构
- Department of Neurosurgery, Yale University, New Haven, CT, USA.
- Department of Hematology and Stem Cell Transplantation, West German Cancer Center (WTZ), National Center for Tumor Diseases (NCT) West, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
- National Institutes of Health, Bethesda, MD, USA.
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
- Preston Robert Tisch Brain Tumor Center at Duke University, Durham, NC, USA.
- Translational Genomics Research Institute, Phoenix, AZ, USA.
- National Cancer Institute, Bethesda, MD, USA.
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
- Walton Centre NHS Foundation Trust, Liverpool, UK.
- Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Health, Detroit, MI, USA.
- Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
- Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
- Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
- Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, USA.
- St Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
- Department of Neurology, IRCCS Ospedale San Raffaele, Milan, Italy.
- Department of Neurology, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.
- Cancer Therapies and Biology Laboratory, Olivia Newton-John Cancer Research Institute, Austin Health, Melbourne, Victoria, Australia.
- Department of Public Health Sciences, Division of Biostatistics and Bioinformatics, Miller School of Medicine, University of Miami, Miami, FL, USA.
- Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
- NORLUX Neuro-Oncology Laboratory, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg.
- Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
- University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA.
- Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
- Department of Neurology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
- Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA.
- Department of Pathology, Prince of Wales Hospital, Hong Kong, China.
- Department of Neurosurgery, Cancer Research Institute, Hypoxia/Ischemia Disease Institute, Seoul National University, Seoul, Republic of Korea.
- Ivy Brain Tumor Center at the Barrow Neurological Institute, Phoenix, AZ, USA.
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Department of Neurosurgery, University of Colorado Anschutz School of Medicine, Aurora, CO, USA.
- Department of Emergency Medicine, University of Colorado Anschutz School of Medicine, Aurora, CO, USA.
- Advanced Institutes of Convergence Technology, Seoul National University, Suwon-si, Republic of Korea.
- Oregon Health & Science University, Portland, OR, USA.
- Neurological Institute, Premier Health and Wright State University School of Medicine, Dayton, OH, USA.
- University of Alabama at Birmingham (UAB), Birmingham, AL, USA.
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
- Department of Cancer Genome Sciences, University of Birmingham, Birmingham, UK.
- Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
- VUmc, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
- Department of Neurosurgery, VUmc, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
- University of California, San Diego, La Jolla, CA, USA.
- Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. frederick.varn@jax.org.
- Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, USA. frederick.varn@jax.org.
- Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA. frederick.varn@jax.org.
- Department of Neurosurgery, Yale University, New Haven, CT, USA. roel.verhaak@yale.edu.
技术路线
['数据/样本：183例IDH突变型胶质瘤患者的纵向收集肿瘤标本（来自GLASS联盟）', '分析：全基因组测序和全外显子组测序，表征纵向标本的遗传驱动因素；验证已知进展基因组标志物（超突变、CDKN2A/B纯合缺失），发现区分星形细胞瘤与少突胶质细胞瘤演化轨迹的遗传改变；分析获得性改变、全基因组变化与患者结局的趋同；关联治疗（替莫唑胺、放疗）与突变特征', '验证：验证已知基因组标志物（超突变和CDKN2A/B纯合缺失）']
最近 5 个完整年度引用趋势
不含 2026 年，仅展示最近 5 个完整年度。
为什么值得关注
编辑短评该研究基于183例IDH突变胶质瘤纵向标本，通过全基因组/外显子测序揭示星形细胞瘤与少突胶质细胞瘤在进展和治疗压力下的基因组演化差异，并验证已知进展标志物。样本量较大、纵向设计及治疗相关突变特征分析增强了发现的可信度。但摘要未报告具体效应量、统计显著性及独立验证队列，结论的普适性仍需进一步确认。