Protein patterns and proteins that identify subtypes of glioblastoma multiforme.
Glioblastoma multiforme (GBM) has been subdivided into two types based on clinical and genetic findings: primary tumors, which arise de novo, and secondary tumors, which progress from lower grade gliomas to GBMs. To analyse this dichotomy at the protein level, we employed selective tissue microdissection to obtain pure populations of tumor cells, which we studied using two-dimensional protein gel electrophoresis (2-DGE) and protein sequencing of select target proteins. Protein patterns were analysed in a blinded manner from the clinical and genetic data. 2-DGE clearly identified two distinct populations of tumors. 2-DGE was reproducible and reliable, as multiple samples analysed from the same patient gave identical results. In addition, we isolated and sequenced 11 proteins that were uniquely expressed in either the primary or the secondary GBMs, but not both. We demonstrate that specific proteomic patterns can be reproducibly identified by two-dimensional gel electrophoresis from limited numbers of selectively procured, microdissected tumor cells and that two patterns of GBMs, primary versus secondary, previously distinguished by clinical and genetic differences, can be recognized at the protein level. Proteins that are expressed distinctively may have important implications for the diagnosis, prognosis, and treatment of patients with GBM.
Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD 20892-1414, USA.
Makoto
M
Furuta
Robert J
RJ
Weil
Alexander O
AO
Vortmeyer
Steve
S
Huang
Jingqi
J
Lei
Tai-Nan
TN
Huang
Youn-Soo
YS
Lee
Deb A
DA
Bhowmick
Irina A
IA
Lubensky
Edward H
EH
Oldfield
Zhengping
Z
Zhuang
D001483:Base Sequence; D017931:DNA Primers; D015180:Electrophoresis, Gel, Two-Dimensional; D005909:Glioblastoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification*; D016609:Neoplasms, Second Primary / Q000145:classification / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D017931:DNA Primers; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human