2021
DOI: 10.1101/2021.05.03.442486
|View full text |Cite
Preprint
|
Sign up to set email alerts
|

Longitudinal analysis of diffuse glioma reveals cell state dynamics at recurrence associated with changes in genetics and the microenvironment

Abstract: To interrogate the factors driving therapy resistance in diffuse glioma, we collected and analyzed RNA and/or DNA sequencing data from temporally separated tumor pairs of 292 adult patients with IDH-wild-type or 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 associated with an increase in prolifera… Show more

Help me understand this report
View published versions

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1

Citation Types

0
5
0

Year Published

2021
2021
2023
2023

Publication Types

Select...
5

Relationship

0
5

Authors

Journals

citations
Cited by 5 publications
(5 citation statements)
references
References 87 publications
0
5
0
Order By: Relevance
“…A recent study by the GLASS consortium found that the classical subtype, enriched with EGFR alteration, was the most plastic to subtype switching upon relapse. 42 Loss of EGFR amplification was significantly associated with a shift in cell state composition, which involves mesenchymal transition. All these findings suggest that the functional dominance of EGFR alteration may be more vulnerable to change during treatment.…”
Section: Discussionmentioning
confidence: 99%
“…A recent study by the GLASS consortium found that the classical subtype, enriched with EGFR alteration, was the most plastic to subtype switching upon relapse. 42 Loss of EGFR amplification was significantly associated with a shift in cell state composition, which involves mesenchymal transition. All these findings suggest that the functional dominance of EGFR alteration may be more vulnerable to change during treatment.…”
Section: Discussionmentioning
confidence: 99%
“…The mesenchymal glioblastoma state is the natural progression of recurring tumors mainly due to the treatments (e.g., irradiation and TMZ) and subsequent chronic brain inflammation (15,16,30,31). Mesenchymal tumors have been reported to exhibit less or none SOX2 dependency contrary to the other subtypes (32)(33)(34).…”
Section: Ses Eradicates Tumorigenicity In Mesenchymal Sox2 − Gbm Canc...mentioning
confidence: 99%
“…One particular technique that has received significant attention and translation is single-cell RNA sequencing (scRNA-seq). 1 In the recent, comprehensive, and elegant review by Khalafallah et al, 2 the authors focus on the clinical implications of scRNA-seq in the management of GBM. The authors describe the evolution of research techniques, beginning at the whole tumor level, using bulk RNA sequencing, progressing to multiregional, tumor bulk RNA-seq, and "zooming in" to scRNA-seq.…”
mentioning
confidence: 99%
“…However, from a clinical perspective, further progress will come from studying individual tumors on a single-cell level along the trajectory of a patient's illness and noting the impact of time and therapies on the molecular heterogeneity. 1 The longitudinal approach could also be used to serially monitor the immune landscape of the tumor as it evolves, thereby informing optimal therapeutic targeting of the immune TME at a specific point in time. For example, there is keen interest in neuro-oncology currently to convert an immunologically suppressive TME, dominated by M2-macrophages, into an M1immunostimulatory state.…”
mentioning
confidence: 99%
See 1 more Smart Citation