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Glioma progression is shaped by genetic evolution and microenvironment interactions.

Publication ,  Journal Article
Varn, FS; Johnson, KC; Martinek, J; Huse, JT; Nasrallah, MP; Wesseling, P; Cooper, LAD; Malta, TM; Wade, TE; Sabedot, TS; Brat, D; Gould, PV ...
Published in: Cell
June 9, 2022

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.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

June 9, 2022

Volume

185

Issue

12

Start / End Page

2184 / 2199.e16

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Neoplasm Recurrence, Local
  • Mutation
  • Isocitrate Dehydrogenase
  • Humans
  • Glioma
  • Genes, p16
  • Evolution, Molecular
  • Developmental Biology
  • Brain Neoplasms
 

Citation

APA
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Varn, F. S., Johnson, K. C., Martinek, J., Huse, J. T., Nasrallah, M. P., Wesseling, P., … GLASS Consortium, . (2022). Glioma progression is shaped by genetic evolution and microenvironment interactions. Cell, 185(12), 2184-2199.e16. https://doi.org/10.1016/j.cell.2022.04.038
Varn, Frederick S., Kevin C. Johnson, Jan Martinek, Jason T. Huse, MacLean P. Nasrallah, Pieter Wesseling, Lee A. D. Cooper, et al. “Glioma progression is shaped by genetic evolution and microenvironment interactions.Cell 185, no. 12 (June 9, 2022): 2184-2199.e16. https://doi.org/10.1016/j.cell.2022.04.038.
Varn FS, Johnson KC, Martinek J, Huse JT, Nasrallah MP, Wesseling P, et al. Glioma progression is shaped by genetic evolution and microenvironment interactions. Cell. 2022 Jun 9;185(12):2184-2199.e16.
Varn, Frederick S., et al. “Glioma progression is shaped by genetic evolution and microenvironment interactions.Cell, vol. 185, no. 12, June 2022, pp. 2184-2199.e16. Pubmed, doi:10.1016/j.cell.2022.04.038.
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 H-E, Pollock S, Goldfarb C, Lee G-H, 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. Glioma progression is shaped by genetic evolution and microenvironment interactions. Cell. 2022 Jun 9;185(12):2184-2199.e16.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

June 9, 2022

Volume

185

Issue

12

Start / End Page

2184 / 2199.e16

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Neoplasm Recurrence, Local
  • Mutation
  • Isocitrate Dehydrogenase
  • Humans
  • Glioma
  • Genes, p16
  • Evolution, Molecular
  • Developmental Biology
  • Brain Neoplasms