Abstract
Original language | English |
---|---|
Pages (from-to) | 2184-2199.e16 |
Journal | Cell |
Volume | 185 |
Issue number | 12 |
DOIs | |
Publication status | Published - 9 Jun 2022 |
Keywords
- genomics
- glioblastoma
- glioma
- hypermutation
- macrophages
- microenvironment
- neurons
- single-cell
- spatial imaging
- treatment resistance
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In: Cell, Vol. 185, No. 12, 09.06.2022, p. 2184-2199.e16.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Glioma progression is shaped by genetic evolution and microenvironment interactions
AU - The GLASS Consortium
AU - Varn, Frederick S.
AU - Johnson, Kevin C.
AU - Martinek, Jan
AU - Huse, Jason T.
AU - Nasrallah, MacLean P.
AU - Wesseling, Pieter
AU - Cooper, Lee A. D.
AU - Malta, Tathiane M.
AU - Wade, Taylor E.
AU - Sabedot, Thais S.
AU - Brat, Daniel
AU - Gould, Peter V.
AU - Wöehrer, Adelheid
AU - Aldape, Kenneth
AU - Ismail, Azzam
AU - Sivajothi, Santhosh K.
AU - Barthel, Floris P.
AU - Kim, Hoon
AU - Kocakavuk, Emre
AU - Ahmed, Nazia
AU - White, Kieron
AU - Datta, Indrani
AU - Moon, Hyo-Eun
AU - Pollock, Steven
AU - Goldfarb, Christine
AU - Lee, Ga-Hyun
AU - Garofano, Luciano
AU - Anderson, Kevin J.
AU - Nehar-Belaid, Djamel
AU - Barnholtz-Sloan, Jill S.
AU - Bakas, Spyridon
AU - Byrne, Annette T.
AU - D'Angelo, Fulvio
AU - Gan, Hui K.
AU - Khasraw, Mustafa
AU - Migliozzi, Simona
AU - Ormond, D. Ryan
AU - Paek, Sun Ha
AU - van Meir, Erwin G.
AU - Walenkamp, Annemiek M. E.
AU - Watts, Colin
AU - Weiss, Tobias
AU - Weller, Michael
AU - Palucka, Karolina
AU - Verhaak, Roel G. W.
AU - Kouwenhoven, Mathilde C. M.
AU - Niers, Johanna M.
AU - Smits, Marion
AU - Westerman, Bart A.
AU - Verhaak, Roel G. W.
AU - Stead, Lucy F.
AU - Poisson, Laila M.
AU - Noushmehr, Houtan
AU - Iavarone, Antonio
N1 - Funding Information: We thank the patients and their families for their generous donations to biomedical research. We gratefully acknowledge the genome technology, single-cell biology, and microscopy services at the Jackson Laboratory for their expert assistance and Z. Reifsnyder (Jackson Laboratory) for the graphic design. We thank R. Puchalski for his helpful suggestions when designing the histopathology validation studies. This work is supported by the National Institutes of Health grants, R01CA237208, R21NS114873, R21CA256575, U2CCA252979 (R.G.W.V.), P30CA034196 (R.G.W.V. and K.P.), R01CA222146 (H.N. L.M.P. and I.D.), P30CA016672, P50CA127001 (J.T.H.), P30CA13148 (E.G.V.M.), U01CA242871, R01NS042645, and U24CA189523 (S.B.); the University of Texas M D Anderson Cancer Center Glioblastoma Moon Shots Program (J.T.H. and D.R.O.); the São Paulo Research Foundation grants 2018/00583-0, 2019/14928-1 (T.M.M.); NCI-FCRDC contract 28XS100 (E.G.V.M.); the Leeds Hospitals Charity grant 9R11/14-11 and UKRI Fellowship MR/T020504/1 (L.F.S.); the Dutch Cancer Society project 11026 (P.W.); European Union's Horizon 2020 GLIOTRAIN initiative (#766069) (A.T.B. and K.W.); the Department of Defense grants CA170278 (H.N. and T.S.S.) and W81XWH1910246 (R.G.W.V.). This work was also supported by generous gifts from the Dabbiere family (R.G.W.V.). Tissue banking within Brain Tumour Northwest is supported by the Sydney Driscoll Neuroscience Foundation and within Leeds by the Yorkshire's Brain Tumour Charity and the OSCAR's Pediatric Brain Tumour Charity. F.P.B. was supported by the JAX Scholar program and the National Cancer Institute (K99CA226387). K.C.J. was the recipient of an American Cancer Society Fellowship (130984-PF-17-141-01-DMC). F.S.V. is supported by the JAX Scholar program and a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. Conceptualization, F.S.V. H.N. A. Iavarone, and R.G.W.V.; methodology, F.S.V.; validation, F.S.V. J.M. J.T.H. M.P.N. P.W. L.A.D.C. D.B. P.V.G. A.W. K.A. A. Ismail, S.K.S. D.N.-B. and K.P.; formal analysis, F.S.V. K.C.J. E.K. N.A. and K.W.; investigation, F.S.V. J.M. S.K.S. G.-L. and C.G.; resources, F.S.V. J.M. J.T.H. P.W. L.A.D.C. T.M.M. A.W. A. Ismail, H.-E.M. S.P. L.G. K.J.A. J.S.B.-S. S.B. H.K.G. D.R.O. S.H.P. E.G.V.M. A.M.E.W. M.W. K.P. L.F.S. L.M.P. and R.G.W.V.; data curation, F.S.V. K.C.J. T.M.M. T.E.W. T.S.S. F.P.B. H.K. N.A. I.D. C.W. D.R.O. L.F.S. and L.M.P.; writing—original draft, F.S.V. R.G.W.V.; writing—review & editing, F.S.V. K.C.J. J.M. J.T.H. P.W. T.M.M. P.V.G. A.W. K.A. F.P.B. E.K. I.D. J.S.B.-S. S.B. H.K.G. M.K. D.R.O. E.G.V.M. A.M.E.W. C.W. T.W. M.W. L.F.S. L.M.P. H.N. A. Iavarone, and R.G.W.V.; supervision, H.N. A. Iavarone, R.G.W.V.; all co-authors and contributors discussed the results and commented on the manuscript. R.G.W.V. is a co-founder of Boundless Bio and a consultant for Stellanova Therapeutics. M.K. has received research funding from AbbVie and Bristol Myers Squibb, and he is on the advisory board for Janssen; he has received honoraria from the Jackson Laboratory. D.R.O. has received funding from Integra and Agios. F.P.B. has performed consulting for Bristol Myers Squibb. M.W. has received research grants from AbbVie, Adastra, Apogenix, Merck, Sharp & Dohme, Novocure, and Quercis and honoraria for lectures or advisory board participation or consulting from AbbVie, Adastra, Basilea, Bristol Meyer Squibb, Celgene, Medac, Merck, Sharp & Dohme, Merck, Nerviano Medical Sciences, Novartis, Orbus, Philogen, Roche, Tocagen, and yMabs. A.M.E.W. reported receiving institutional financial support for an advisory role from Polyphor, IPSEN, Karyopharm, and Novartis; unrestricted research grants from IPSEN and Novartis; and study budgets from AbbVie, BMS, Genzyme, Karyopharm Therapeutics, and Roche, all outside the submitted work. H.K.G. has performed consulting for AbbVie, and he is a member of the speaker bureau for AbbVie and Igynta. K.P. is a scientific advisory board member and owns stock in Cue BioPharma. Funding Information: We thank the patients and their families for their generous donations to biomedical research. We gratefully acknowledge the genome technology, single-cell biology, and microscopy services at the Jackson Laboratory for their expert assistance and Z. Reifsnyder (Jackson Laboratory) for the graphic design. We thank R. Puchalski for his helpful suggestions when designing the histopathology validation studies. This work is supported by the National Institutes of Health grants, R01CA237208 , R21NS114873 , R21CA256575 , U2CCA252979 (R.G.W.V.), P30CA034196 (R.G.W.V. and K.P.), R01CA222146 (H.N., L.M.P., and I.D.), P30CA016672 , P50CA127001 (J.T.H.), P30CA13148 (E.G.V.M.), U01CA242871 , R01NS042645 , and U24CA189523 (S.B.); the University of Texas M D Anderson Cancer Center Glioblastoma Moon Shots Program (J.T.H. and D.R.O.); the São Paulo Research Foundation grants 2018/00583-0 , 2019/14928-1 (T.M.M.); NCI - FCRDC contract 28XS100 (E.G.V.M.); the Leeds Hospitals Charity grant 9R11/14-11 and UKRI Fellowship MR/T020504/1 ( L.F.S. ); the Dutch Cancer Society project 11026 (P.W.); European Union’s Horizon 2020 GLIOTRAIN initiative (# 766069 ) (A.T.B. and K.W.); the Department of Defense grants CA170278 (H.N. and T.S.S.) and W81XWH1910246 (R.G.W.V.). This work was also supported by generous gifts from the Dabbiere family (R.G.W.V.). Tissue banking within Brain Tumour Northwest is supported by the Sydney Driscoll Neuroscience Foundation and within Leeds by the Yorkshire's Brain Tumour Charity and the OSCAR's Pediatric Brain Tumour Charity . F.P.B. was supported by the JAX Scholar program and the National Cancer Institute ( K99CA226387 ). K.C.J. was the recipient of an American Cancer Society Fellowship ( 130984-PF-17-141-01-DMC ). F.S.V. is supported by the JAX Scholar program and a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research . Publisher Copyright: © 2022 Elsevier Inc.
PY - 2022/6/9
Y1 - 2022/6/9
N2 - The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions were associated with an increase in proliferating neoplastic cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their neoplastic cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a myeloid cell state defined by specific ligand-receptor interactions with neoplastic cells. Collectively, these recurrence-associated phenotypes represent potential targets to alter disease progression.
AB - The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions were associated with an increase in proliferating neoplastic cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their neoplastic cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a myeloid cell state defined by specific ligand-receptor interactions with neoplastic cells. Collectively, these recurrence-associated phenotypes represent potential targets to alter disease progression.
KW - genomics
KW - glioblastoma
KW - glioma
KW - hypermutation
KW - macrophages
KW - microenvironment
KW - neurons
KW - single-cell
KW - spatial imaging
KW - treatment resistance
UR - http://www.scopus.com/inward/record.url?scp=85131903367&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cell.2022.04.038
DO - https://doi.org/10.1016/j.cell.2022.04.038
M3 - Article
C2 - 35649412
SN - 0092-8674
VL - 185
SP - 2184-2199.e16
JO - Cell
JF - Cell
IS - 12
ER -