| Literature DB >> 35649412 |
Frederick S Varn1, Kevin C Johnson1, Jan Martinek1, Jason T Huse2, MacLean P Nasrallah3, Pieter Wesseling4, Lee A D Cooper5, Tathiane M Malta6, Taylor E Wade1, Thais S Sabedot7, Daniel Brat5, Peter V Gould8, Adelheid Wöehrer9, Kenneth Aldape10, Azzam Ismail11, Santhosh K Sivajothi1, Floris P Barthel12, Hoon Kim13, Emre Kocakavuk14, Nazia Ahmed15, Kieron White16, Indrani Datta17, Hyo-Eun Moon18, Steven Pollock15, Christine Goldfarb1, Ga-Hyun Lee1, Luciano Garofano19, Kevin J Anderson1, Djamel Nehar-Belaid1, Jill S Barnholtz-Sloan20, Spyridon Bakas21, Annette T Byrne16, Fulvio D'Angelo19, Hui K Gan22, Mustafa Khasraw23, Simona Migliozzi19, D Ryan Ormond24, Sun Ha Paek18, Erwin G Van Meir25, Annemiek M E Walenkamp26, Colin Watts27, Tobias Weiss28, Michael Weller28, Karolina Palucka1, Lucy F Stead15, Laila M Poisson17, Houtan Noushmehr7, Antonio Iavarone29, Roel G W Verhaak30.
Abstract
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.Entities:
Keywords: genomics; glioblastoma; glioma; hypermutation; macrophages; microenvironment; neurons; single-cell; spatial imaging; treatment resistance
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Year: 2022 PMID： 35649412 PMCID： PMC9189056 DOI： 10.1016/j.cell.2022.04.038
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850