Spatial and temporal genomic evolution in glioblastoma

Tumor heterogeneity is a challenging barrier to successful targeted therapy in glioblastoma. Identifying the mechanisms that drive cancer cells as they genetically evolve and adapt in response to treatment is a vital goal of modern cancer research. Analysis of sequencing data provides a method for uncovering the mechanisms sustaining tumor heterogeneity and driving evolution. Here, we analyzed genomic profiles of GBM biopsies taken from pre- and post-treatment GBMs (with matched germline controls), to understand 1) the intratumoral clonal compositions of primary GBM and 2) how GBM responds to therapeutic intervention. Our results provide a molecular portrait of GBM recurrence.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

7 Datasets 10 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001001109	None	Illumina HiSeq 2000	46
EGAD00001001110	None	Illumina HiSeq 2000	46
EGAD00001001111	None	Illumina HiSeq 2000	46
EGAD00001001112	None	Illumina HiSeq 2000	46
EGAD00001001113	None	Illumina HiSeq 2000	46
EGAD00010000654	Control samples using SNP 6.0 Arrays		1
EGAD00010000656	Case samples using SNP 6.0 Array		1

Publications	Citations
Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution. Kim H, Zheng S, Amini SS, Virk SM, Mikkelsen T, Brat DJ, Grimsby J, Sougnez C, Muller F, Hu J, Sloan AE, Cohen ML, Van Meir EG, Scarpace L, Laird PW, Weinstein JN, Lander ES, Gabriel S, Getz G, Meyerson M, Chin L, Barnholtz-Sloan JS, Verhaak RG. Genome Res 25: 2015 316-327	254
Clonal evolution of glioblastoma under therapy. Wang J, Cazzato E, Ladewig E, Frattini V, Rosenbloom DI, Zairis S, Abate F, Liu Z, Elliott O, Shin YJ, Lee JK, Lee IH, Park WY, Eoli M, Blumberg AJ, Lasorella A, Nam DH, Finocchiaro G, Iavarone A, Rabadan R. Nat Genet 48: 2016 768-776	420
Between-region genetic divergence reflects the mode and tempo of tumor evolution. Sun R, Hu Z, Sottoriva A, Graham TA, Harpak A, Ma Z, Fischer JM, Shibata D, Curtis C. Nat Genet 49: 2017 1015-1024	78
Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Wang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L, deCarvalho AC, Lyu S, Li P, Li Y, Barthel F, Cho HJ, Lin YH, Satani N, Martinez-Ledesma E, Zheng S, Chang E, Sauvé CG, Olar A, Lan ZD, Finocchiaro G, Phillips JJ, Berger MS, Gabrusiewicz KR, Wang G, Eskilsson E, Hu J, Mikkelsen T, DePinho RA, Muller F, Heimberger AB, Sulman EP, Nam DH, Verhaak RGW. Cancer Cell 32: 2017 42-56.e6	966
Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy. Caswell-Jin JL, McNamara K, Reiter JG, Sun R, Hu Z, Ma Z, Ding J, Suarez CJ, Tilk S, Raghavendra A, Forte V, Chin SF, Bardwell H, Provenzano E, Caldas C, Lang J, West R, Tripathy D, Press MF, Curtis C. Nat Commun 10: 2019 657	31
Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy. Gromeier M, Brown MC, Zhang G, Lin X, Chen Y, Wei Z, Beaubier N, Yan H, He Y, Desjardins A, Herndon JE, Varn FS, Verhaak RG, Zhao J, Bolognesi DP, Friedman AH, Friedman HS, McSherry F, Muscat AM, Lipp ES, Nair SK, Khasraw M, Peters KB, Randazzo D, Sampson JH, McLendon RE, Bigner DD, Ashley DM. Nat Commun 12: 2021 352	71
Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities. Garofano L, Migliozzi S, Oh YT, D'Angelo F, Najac RD, Ko A, Frangaj B, Caruso FP, Yu K, Yuan J, Zhao W, Di Stefano AL, Bielle F, Jiang T, Sims P, Suvà ML, Tang F, Su XD, Ceccarelli M, Sanson M, Lasorella A, Iavarone A. Nat Cancer 2: 2021 141-156	146
Glioma progression is shaped by genetic evolution and microenvironment interactions. Varn FS, Johnson KC, Martinek J, Huse JT, Nasrallah MP, Wesseling P, Cooper LAD, Malta TM, Wade TE, Sabedot TS, Brat D, Gould PV, Wöehrer A, Aldape K, Ismail A, Sivajothi SK, Barthel FP, Kim H, Kocakavuk E, Ahmed N, White K, Datta I, Moon HE, Pollock S, Goldfarb C, Lee GH, Garofano L, Anderson KJ, Nehar-Belaid D, Barnholtz-Sloan JS, Bakas S, Byrne AT, D'Angelo F, Gan HK, Khasraw M, Migliozzi S, Ormond DR, Paek SH, Van Meir EG, Walenkamp AME, Watts C, Weiss T, Weller M, Palucka K, Stead LF, Poisson LM, Noushmehr H, Iavarone A, Verhaak RGW, GLASS Consortium. Cell 185: 2022 2184-2199.e16	154
Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild-type primary glioblastoma. Nam Y, Koo H, Yang Y, Shin S, Zhu Z, Kim D, Cho HJ, Mu Q, Choi SW, Sa JK, Seo YJ, Kim Y, Lee K, Oh JW, Kwon YJ, Park WY, Kong DS, Seol HJ, Lee JI, Park CK, Lee HW, Yoon Y, Wang J. Genome Med 15: 2023 16	6
Glioblastoma heterogeneity at single cell resolution. Eisenbarth D, Wang YA. Oncogene 42: 2023 2155-2165	27