TY - JOUR
T1 - Large Scale Identification of Variant Proteins in Glioma Stem Cells
AU - Mostovenko, Ekaterina
AU - Végvári, Ákos
AU - Rezeli, Melinda
AU - Lichti, Cheryl F.
AU - Fenyö, David
AU - Wang, Qianghu
AU - Lang, Frederick F.
AU - Sulman, Erik P.
AU - Sahlin, K. Barbara
AU - Marko-Varga, György
AU - Nilsson, Carol L.
N1 - Funding Information:
D.F. was supported by the National Cancer Institute (NCI) CPTAC Award U24 CA210972, Contract 13XS068 from Leidos Biomedical Research, Inc., and by a grant from the Shifrin-Myers Breast Cancer Discovery Fund. F.F.L and E.P.S. were supported by MD Anderson Brain SPORE P50-CA127001, E.P.S. was supported by R01-CA1902, and E.P.S. and Q.W. were supported by the National Brain Tumor Society Defeat GBM project. C.L.N. acknowledges the support of the University of Texas Medical Branch, The University of Texas M. D. Anderson Cancer Center, The Cancer Prevention Research Institute of Texas (RML1122), the Center of Excellence in Biological and Medical Mass Spectrometry, and Lund University.
Funding Information:
*E-mail: [email protected]. ORCID Melinda Rezeli: 0000-0003-4373-5616 Carol L. Nilsson: 0000-0002-2838-8751 Author Contributions E.M., C.F.L., D.F., K.B.S., and Q.W. critically analyzed ‘omics data sets. F.F.L. and E.P.S. supplied the samples and provided insight into neuro-oncological aspects related to the findings. E.M., M.R., C.F.L., G.M.-V., and C.L.N. designed the experiments. A.V. created the custom SAV database. All coauthors contributed to the writing of this report. Funding D.F. was supported by the National Cancer Institute (NCI) CPTAC Award U24 CA210972, Contract 13XS068 from Leidos Biomedical Research, Inc., and by a grant from the Shifrin-Myers Breast Cancer Discovery Fund. F.F.L and E.P.S. were supported by MD Anderson Brain SPORE P50-CA127001, E.P.S. was supported by R01-CA1902, and E.P.S. and Q.W. were supported by the National Brain Tumor Society Defeat GBM project. C.L.N. acknowledges the support of the University of Texas Medical Branch, The University of Texas M. D. Anderson Cancer Center, The Cancer Prevention Research Institute of Texas (RML1122), the Center of Excellence in Biological and Medical Mass Spectrometry, and Lund University. Notes The authors declare no competing financial interest.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2018/1/17
Y1 - 2018/1/17
N2 - Glioblastoma (GBM), the most malignant of primary brain tumors, is a devastating and deadly disease, with a median survival of 14 months from diagnosis, despite standard regimens of radical brain tumor surgery, maximal safe radiation, and concomitant chemotherapy. GBM tumors nearly always re-emerge after initial treatment and frequently display resistance to current treatments. One theory that may explain GBM re-emergence is the existence of glioma stemlike cells (GSCs). We sought to identify variant protein features expressed in low passage GSCs derived from patient tumors. To this end, we developed a proteomic database that reflected variant and nonvariant sequences in the human proteome, and applied a novel retrograde proteomic workflow, to identify and validate the expression of 126 protein variants in 33 glioma stem cell strains. These newly identified proteins may harbor a subset of novel protein targets for future development of GBM therapy.
AB - Glioblastoma (GBM), the most malignant of primary brain tumors, is a devastating and deadly disease, with a median survival of 14 months from diagnosis, despite standard regimens of radical brain tumor surgery, maximal safe radiation, and concomitant chemotherapy. GBM tumors nearly always re-emerge after initial treatment and frequently display resistance to current treatments. One theory that may explain GBM re-emergence is the existence of glioma stemlike cells (GSCs). We sought to identify variant protein features expressed in low passage GSCs derived from patient tumors. To this end, we developed a proteomic database that reflected variant and nonvariant sequences in the human proteome, and applied a novel retrograde proteomic workflow, to identify and validate the expression of 126 protein variants in 33 glioma stem cell strains. These newly identified proteins may harbor a subset of novel protein targets for future development of GBM therapy.
KW - GBM
KW - Glioblastoma
KW - bioinformatics
KW - parallel reaction monitoring
KW - precision medicine
KW - protein quantification
KW - protein single amino acid variants
KW - proteomics
KW - targeted mass spectrometry
KW - transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85040656011&partnerID=8YFLogxK
U2 - 10.1021/acschemneuro.7b00362
DO - 10.1021/acschemneuro.7b00362
M3 - Article
C2 - 29254333
AN - SCOPUS:85040656011
SN - 1948-7193
VL - 9
SP - 73
EP - 79
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 1
ER -