Protein patterns and proteins that identify subtypes of glioblastoma multiforme

• Published in: Oncogene Vol. 23; no. 40; pp. 6806 - 6814
• Main Authors: FURUTA, Makoto, WEIL, Robert J, ZHENGPING ZHUANG, VORTMEYER, Alexander O, HUANG, Steve, JINGQI LEI, HUANG, Tai-Nan, LEE, Youn-Soo, BHOWMICK, Deb A, LUBENSKY, Irina A, OLDFIELD, Edward H
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 02.09.2004; Nature Publishing Group
• Subjects: Apoptosis; Base Sequence; Biological and medical sciences; Brain cancer; Cell cycle; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DNA Primers; Electrophoresis, Gel, Two-Dimensional; Fundamental and applied biological sciences. Psychology; Gel electrophoresis; Glioblastoma; Glioblastoma - classification; Glioblastoma - genetics; Glioblastoma - pathology; Glioma; Growth factors; Humans; Medical prognosis; Medical sciences; Molecular and cellular biology; Mutation - genetics; Neoplasm Proteins - genetics; Neoplasm Proteins - isolation & purification; Neoplasms, Second Primary - classification; Neoplasms, Second Primary - genetics; Neoplasms, Second Primary - pathology; Neurological disorders; Neurology; Patients; Phosphoric Monoester Hydrolases - genetics; Polymerase Chain Reaction; Proteins; Proteomics; PTEN Phosphohydrolase; Tumor cells; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Proteins - genetics; Tumors; Tumors of the nervous system. Phacomatoses; United States > US; Nervous system diseases; Microdissection; protein sequencing; Identification; Malignant tumor; Carcinogenesis; Glioblastoma multiforme; Protein; Malignant glioma; Central nervous system disease; Two dimensional electrophoresis; Mass spectrometry; Sequencing; Astrocytoma; two-dimensional gel electrophoresis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1207770

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.