PMID- 36920905
OWN - NLM
STAT- MEDLINE
DCOM- 20230403
LR  - 20230421
IS  - 2211-1247 (Electronic)
VI  - 42
IP  - 3
DP  - 2023 Mar 28
TI  - Single-cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune 
      infiltration in glioblastoma.
PG  - 112235
LID - S2211-1247(23)00246-2 [pii]
LID - 10.1016/j.celrep.2023.112235 [doi]
AB  - Glioblastoma (GBM) is the most aggressive brain tumor, with a median survival of 
       approximately 15 months. Targeted approaches have not been successful in this tumor type due 
      to the large extent of intratumor heterogeneity. Mosaic amplification of 
      oncogenes suggests that multiple genetically distinct clones are present in each 
      tumor. To uncover the relationships between genetically diverse subpopulations of 
      GBM cells and their native tumor microenvironment, we employ highly multiplexed 
      spatial protein profiling coupled with single-cell spatial mapping of 
      fluorescence in situ hybridization (FISH) for EGFR, CDK4, and PDGFRA. Single-cell 
      FISH analysis of a total of 35,843 single nuclei reveals that tumors in which 
      amplifications of EGFR and CDK4 more frequently co-occur in the same cell exhibit 
      higher infiltration of CD163(+) immunosuppressive macrophages. Our results 
      suggest that high-throughput assessment of genomic alterations at the single-cell 
      level could provide a measure for predicting the immune state of GBM.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Walentynowicz, Kacper A
AU  - Walentynowicz KA
AD  - Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for 
      Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular 
      Medicine, Scripps Research, Jupiter, FL, USA.
FAU - Engelhardt, Dalit
AU  - Engelhardt D
AD  - Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA, USA; 
      Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA; 
      Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, 
      MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, 
      Cambridge, MA, USA.
FAU - Cristea, Simona
AU  - Cristea S
AD  - Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA; 
      Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, 
      MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, 
      Cambridge, MA, USA; Department of Medical Oncology, Harvard Medical School, 
      Boston, MA, USA.
FAU - Yadav, Shreya
AU  - Yadav S
AD  - Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for 
      Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular 
      Medicine, Scripps Research, Jupiter, FL, USA.
FAU - Onubogu, Ugoma
AU  - Onubogu U
AD  - Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for 
      Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular 
      Medicine, Scripps Research, Jupiter, FL, USA; The Skaggs Graduate School of 
      Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA, 
      USA.
FAU - Salatino, Roberto
AU  - Salatino R
AD  - Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for 
      Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular 
      Medicine, Scripps Research, Jupiter, FL, USA; The Skaggs Graduate School of 
      Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA, 
      USA.
FAU - Maerken, Melanie
AU  - Maerken M
AD  - Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for 
      Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular 
      Medicine, Scripps Research, Jupiter, FL, USA.
FAU - Vincentelli, Cristina
AU  - Vincentelli C
AD  - Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL, USA.
FAU - Jhaveri, Aashna
AU  - Jhaveri A
AD  - Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Geisberg, Jacob
AU  - Geisberg J
AD  - Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - McDonald, Thomas O
AU  - McDonald TO
AD  - Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA, USA; 
      Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA; 
      Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, 
      MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, 
      Cambridge, MA, USA.
FAU - Michor, Franziska
AU  - Michor F
AD  - Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA, USA; 
      Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA; 
      Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, 
      MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, 
      Cambridge, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA; 
      The Ludwig Center at Harvard, Boston, MA, USA. Electronic address: 
      michor@jimmy.harvard.edu.
FAU - Janiszewska, Michalina
AU  - Janiszewska M
AD  - Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for 
      Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular 
      Medicine, Scripps Research, Jupiter, FL, USA; The Skaggs Graduate School of 
      Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA, 
      USA. Electronic address: mjaniszewska@ufl.edu.
LA  - eng
GR  - R00 CA201606/CA/NCI NIH HHS/United States
GR  - K99 CA201606/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230314
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.10.1 (EGFR protein, human)
SB  - IM
MH  - Humans
MH  - *Glioblastoma/pathology
MH  - Gene Amplification
MH  - In Situ Hybridization, Fluorescence
MH  - ErbB Receptors/genetics/metabolism
MH  - Oncogenes
MH  - *Brain Neoplasms/metabolism
MH  - Tumor Microenvironment
MH  - Cyclin-Dependent Kinase 4/genetics/metabolism
PMC - PMC10114292
MID - NIHMS1887296
OTO - NOTNLM
OT  - CDK4
OT  - CP: Cancer
OT  - EGFR
OT  - genetic heterogeneity
OT  - glioblastoma
OT  - tumor microenvironment
COIS- Declaration of interests M.J. is a member of a scientific advisory board at 
      ResistanceBio (formerly Viosera Therapeutics).
EDAT- 2023/03/16 06:00
MHDA- 2023/04/03 06:42
PMCR- 2023/04/19
CRDT- 2023/03/15 13:36
PHST- 2021/09/22 00:00 [received]
PHST- 2022/12/20 00:00 [revised]
PHST- 2023/02/23 00:00 [accepted]
PHST- 2023/04/03 06:42 [medline]
PHST- 2023/03/16 06:00 [pubmed]
PHST- 2023/03/15 13:36 [entrez]
PHST- 2023/04/19 00:00 [pmc-release]
AID - S2211-1247(23)00246-2 [pii]
AID - 10.1016/j.celrep.2023.112235 [doi]
PST - ppublish
SO  - Cell Rep. 2023 Mar 28;42(3):112235. doi: 10.1016/j.celrep.2023.112235. Epub 2023 
      Mar 14.