Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas

被引：295

作者：

Ryall, Scott ^{[1
,2
]}

Zapotocky, Michal ^{[1
,3
,4
,5
]}

Fukuoka, Kohei ^{[1
,3
]}

Nobre, Liana ^{[1
,3
]}

Stucklin, Ana Guerreiro ^{[1
,3
,6
]}

Bennett, Julie ^{[1
,3
]}

Siddaway, Robert ^{[1
]}

Li, Christopher ^{[1
,2
]}

Pajovic, Sanja ^{[1
]}

Arnoldo, Anthony ^{[7
]}

Kowalski, Paul E. ^{[7
]}

Johnson, Monique ^{[7
]}

Sheth, Javal ^{[1
,7
]}

Lassaletta, Alvaro ^{[1
,3
,8
]}

Tatevossian, Ruth G. ^{[9
]}

Orisme, Wilda ^{[9
]}

Qaddoumi, Ibrahim ^{[10
]}

Surrey, Lea F. ^{[11
,12
]}

Li, Marilyn M. ^{[11
]}

Waanders, Angela J. ^{[12
,13
,14
,15
]}

Gilheeney, Stephen ^{[16
]}

Rosenblum, Marc ^{[17
]}

Bale, Tejus ^{[17
]}

Tsang, Derek S. ^{[18
,19
]}

Laperriere, Normand ^{[18
,19
]}

Kulkarni, Abhaya ^{[20
,21
]}

Ibrahim, George M. ^{[20
,21
]}

Drake, James ^{[20
,21
]}

Dirks, Peter ^{[1
,2
,21
]}

Taylor, Michael D. ^{[1
,2
,21
]}

Rutka, James T. ^{[1
,2
,21
]}

Laughlin, Suzanne ^{[22
,23
]}

Shroff, Manohar ^{[22
,23
]}

Shago, Mary ^{[2
,7
]}

Hazrati, Lili-Naz ^{[2
,24
]}

D'Arcy, Colleen ^{[2
,24
,25
]}

Ramaswamy, Vijay ^{[1
,3
,26
]}

Bartels, Ute ^{[3
,26
]}

Huang, Annie ^{[1
,2
,3
]}

Bouffet, Eric ^{[3
,26
]}

Karajannis, Matthias A. ^{[16
]}

Santi, Mariarita ^{[11
,12
]}

Ellison, David W. ^{[9
]}

Tabori, Uri ^{[1
,3
,27
]}

Hawkins, Cynthia ^{[1
,2
,24
]}

机构：

[1] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, 555 Univ Ave, Toronto, ON M5G 1X8, Canada

[2] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[3] Hosp Sick Children, Dept Haematol Oncol, Toronto, ON, Canada

[4] Charles Univ Prague, Fac Med 2, Prague, Czech Republic

[5] Univ Hosp Moto, Prague, Czech Republic

[6] Univ Childrens Hosp Zurich, Childrens Res Ctr, Zurich, Switzerland

[7] Hosp Sick Children, Dept Paediat Lab Med, Toronto, ON, Canada

[8] Hosp Univ Nino Jesus, Dept Pediat Hematol & Oncol, Madrid, Spain

[9] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA

[10] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA

[11] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[12] Childrens Hosp Philadelphia, Dept Genom Diagnost, Philadelphia, PA 19104 USA

[13] Childrens Hosp Philadelphia, Ctr Data Driven Discovery Biomed, Philadelphia, PA 19104 USA

[14] Ann & Robert H Lurie Childrens Hosp Chicago, Dept Hematol Oncol & Stem Cell Transplant, Chicago, IL 60611 USA

[15] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA

[16] Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA

[17] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[18] Univ Hlth Network, Princess Margaret Canc Ctr, Radiat Med Program, Toronto, ON, Canada

[19] Univ Toronto, Fac Med, Dept Radiat Oncol, Toronto, ON, Canada

[20] Univ Toronto, Dept Surg, Toronto, ON, Canada

[21] Hosp Sick Children, Dept Neurosurg, Toronto, ON, Canada

[22] Hosp Sick Children, Dept Radiol, Toronto, ON, Canada

[23] Univ Toronto, Dept Med Imaging, Toronto, ON, Canada

[24] Hosp Sick Children, Dept Pathol, Toronto, ON, Canada

[25] Alfred Hosp, Dept Anat Pathol, Prahran, Vic, Australia

[26] Univ Toronto, Dept Paediat, Toronto, ON, Canada

[27] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

来源：

CANCER CELL | 2020年 / 37卷 / 04期

基金：

加拿大健康研究院;

关键词：

INTRINSIC PONTINE GLIOMA; MAPK PATHWAY ACTIVATION; GENETIC ALTERATIONS; GENOMIC ANALYSIS; NERVOUS-SYSTEM; IDH2; MUTATIONS; BRAF; TUMORS; ABERRATIONS; FUSION;

D O I：

10.1016/j.ccell.2020.03.011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. Eighty-four percent of cases harbored a driver alteration, while those without an identified alteration also often exhibited upregulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared with SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement.

引用

页码：569 / +

页数：20

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