Epigenetic Alterations of Repeated Relapses in Patient-matched Childhood Ependymomas

被引：0

作者：

Sibo Zhao

Jia Li

Huiyuan Zhang

Lin Qi

Yuchen Du

Mari Kogiso

Frank K. Braun

Sophie Xiao

Yulun Huang

Jianfang Li

Wan-Yee Teo

Holly Lindsay

Patricia Baxter

Jack M. F. Su

Adekunle Adesina

Miklós Laczik

Paola Genevini

Anne-Clemence Veillard

Sol Schvartzman

Geoffrey Berguet

Shi-Rong Ding

Liping Du

Clifford Stephan

Jianhua Yang

Peter J. A. Davies

Xinyan Lu

Murali Chintagumpala

Donald William Parsons

Laszlo Perlaky

Yun-Fei Xia

Tsz-Kwong Man

Yun Huang

Deqiang Sun

Xiao-Nan Li

机构：

[1] Texas Children’s Hospital,Pre

[2] Baylor College of Medicine,clinical Neuro

[3] Texas Children’s Hospital,oncology Research Program

[4] Baylor College of Medicine,Texas Children’s Cancer Center

[5] Cook Children’s Medical Center,Jane and John Justin Neurosciences Center

[6] Cook Children’s Medical Center,Hematology and Oncology Center

[7] Texas A&M University,Center for Epigenetics & Disease Prevention

[8] Texas A&M University,Center for Translational Cancer Research, Institute of Biosciences and Technology

[9] Guangzhou Institute of Respiratory Health,State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease

[10] the First Affiliated Hospital of Guangzhou Medical University; and Guangzhou Laboratory,Program of Precision Medicine PDOX Modeling of Pediatric Tumors, Division of Hematology

[11] Bioland,Oncology, Neuro

[12] Northwestern University Feinberg School of Medicine,Oncology & Stem Cell transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago; Department of Pediatrics

[13] the First Affiliated Hospital,Department of Neurosurgery and Brain and Nerve Research Laboratory

[14] and Department of Neurosurgery,Humphrey Oei Institute of Cancer Research

[15] Dushu Lake Hospital,Cancer and Stem Cell Biology Program

[16] Suzhou Medical College,Department of Pathology, Texas Children’s Hospital

[17] Soochow University,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine; Department of Radiation

[18] National Cancer Center Singapore,Clinical Cytogenetic Laboratory, Department of Pathology

[19] Duke-NUS Medical School Singapore,undefined

[20] KK Women’s & Children’s Hospital Singapore,undefined

[21] Institute of Molecular and Cell Biology,undefined

[22] A*STAR,undefined

[23] Baylor College of Medicine,undefined

[24] Epigenetic Services,undefined

[25] Sun Yat-sen University Cancer Center,undefined

[26] Northwestern University Feinberg School of Medicine,undefined

来源：

Nature Communications | / 13卷 / 1期

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摘要：

Recurrence is frequent in pediatric ependymoma (EPN). Our longitudinal integrated analysis of 30 patient-matched repeated relapses (3.67 ± 1.76 times) over 13 years (5.8 ± 3.8) reveals stable molecular subtypes (RELA and PFA) and convergent DNA methylation reprogramming during serial relapses accompanied by increased orthotopic patient derived xenograft (PDX) (13/27) formation in the late recurrences. A set of differentially methylated CpGs (DMCs) and DNA methylation regions (DMRs) are found to persist in primary and relapse tumors (potential driver DMCs) and are acquired exclusively in the relapses (potential booster DMCs). Integrating with RNAseq reveals differentially expressed genes regulated by potential driver DMRs (CACNA1H, SLC12A7, RARA in RELA and HSPB8, GMPR, ITGB4 in PFA) and potential booster DMRs (PLEKHG1 in RELA and NOTCH, EPHA2, SUFU, FOXJ1 in PFA tumors). DMCs predicators of relapse are also identified in the primary tumors. This study provides a high-resolution epigenetic roadmap of serial EPN relapses and 13 orthotopic PDX models to facilitate biological and preclinical studies.

引用

共 108 条

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