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Integrated Proteogenomic Characterization across Major Histological Types of Pediatric Brain Cancer
Francesca Petralia ,
Nicole Tignor ,
Boris Reva ,
Mateusz Koptyra ,
Shrabanti Chowdhury ,
Dmitry Rykunov ,
Azra Krek ,
Weiping Ma ,
Yuankun Zhu ,
Jiayi Ji ,
Anna Calinawan ,
Jeffrey R. Whiteaker ,
Antonio Colaprico ,
Vasileios Stathias ,
Tatiana Omelchenko ,
Xiaoyu Song ,
Pichai Raman ,
Yiran Guo ,
Miguel A. Brown ,
Richard G. Ivey ,
John Szpyt ,
Sanjukta Guha Thakurta ,
Marina A. Gritsenko ,
Karl K. Weitz ,
Gonzalo Lopez ,
Selim Kalayci ,
Zeynep H. Gümüş ,
Seungyeul Yoo ,
Felipe da Veiga Leprevost ,
Hui-Yin Chang ,
Karsten Krug ,
Lizabeth Katsnelson ,
Ying Wang ,
Jacob J. Kennedy ,
Uliana J. Voytovich ,
Lei Zhao ,
Krutika S. Gaonkar ,
Brian M. Ennis ,
Bo Zhang ,
Valerie Baubet ,
Lamiya Tauhid ,
Jena V. Lilly ,
Jennifer L. Mason ,
Bailey Farrow ,
Nathan Young ,
Sarah Leary ,
Jamie Moon ,
Vladislav A. Petyuk ,
Javad Nazarian ,
Nithin D. Adappa ,
James N. Palmer ,
Robert M. Lober ,
Samuel Rivero-Hinojosa ,
Liang-Bo Wang ,
Joshua M. Wang ,
Matilda Broberg ,
Rosalie K. Chu ,
Ronald J. Moore ,
Matthew E. Monroe ,
Rui Zhao ,
Richard D. Smith ,
Jun Zhu ,
Ana I. Robles ,
Mehdi Mesri ,
Emily Boja ,
Tara Hiltke ,
Henry Rodriguez ,
Bing Zhang ,
Eric E. Schadt ,
D.R. Mani ,
Li Ding ,
Antonio Iavarone ,
Maciej Wiznerowicz ,
Stephan Schürer ,
Xi S. Chen ,
Allison P. Heath ,
Jo Lynne Rokita ,
Alexey I. Nesvizhskii ,
David Fenyö ,
Karin D. Rodland ,
Tao Liu ,
Steven P. Gygi ,
Amanda G. Paulovich ,
Adam C. Resnick ,
Phillip B. Storm ,
Brian R. Rood ,
Pei Wang ,
Alicia Francis ,
Allison M. Morgan ,
Angela J. Waanders ,
Angela N. Viaene ,
Anna Maria Buccoliero ,
Arul M. Chinnaiyan ,
Carina A. Leonard ,
Cassie N. Kline ,
Chiara Caporalini ,
Christopher R. Kinsinger ,
Chunde Li ,
David E. Kram ,
Derek Hanson ,
Elizabeth Appert ,
Emily A. Kawaler ,
Eric H. Raabe ,
Eric M. Jackson ,
Jeffrey P. Greenfield ,
Gabrielle S. Stone ,
Gad Getz ,
Gerald Grant ,
Guo Ci Teo ,
Ian F. Pollack ,
Jason E. Cain ,
Jessica B. Foster ,
Joanna J. Phillips ,
July E. Palma ,
Karen A. Ketchum ,
Kelly V. Ruggles ,
Lili Blumenberg ,
Macintosh Cornwell ,
Mahdi Sarmady ,
Marcin J. Domagalski ,
Marcin P. Cieślik ,
Mariarita Santi ,
Marilyn M. Li ,
Matthew J. Ellis ,
Matthew A. Wyczalkowski ,
Meghan Connors ,
Mirko Scagnet ,
Nalin Gupta ,
Nathan J. Edwards ,
Nicholas A. Vitanza ,
Olena M. Vaske ,
Oren Becher ,
Peter B. McGarvey ,
Ron Firestein ,
Sabine Mueller ,
Samuel G. Winebrake ,
Saravana Mohan Dhanasekaran ,
Shuang Cai ,
Sonia Partap ,
Tatiana Patton ,
Toan Le ,
Travis D. Lorentzen ,
Wenke Liu ,
William E. Bocik
November 2020
November 2020
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Abstract
<p class="first" id="d2776472e1007">We report a comprehensive proteogenomics analysis,
including whole-genome sequencing,
RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across
7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma
(32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma
(16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological
themes that span histological boundaries, suggesting that treatments used for one
histological type may be applied effectively to other tumors sharing similar proteomics
features. Immune landscape characterization reveals diverse tumor microenvironments
across and within diagnoses. Proteomics data further reveal functional effects of
somatic mutations and copy number variations (CNVs) not evident in transcriptomics
data. Kinase-substrate association and co-expression network analysis identify important
biological mechanisms of tumorigenesis. This is the first large-scale proteogenomics
analysis across traditional histological boundaries to uncover foundational pediatric
brain tumor biology and inform rational treatment selection.
</p>