Rhabdoid glioblastoma is distinguishable from classical glioblastoma by cytogenetics and molecular genetics.
The clinicopathologic and molecular genetic features of 5 cases of rhabdoid glioblastoma, an extremely rare variant of glioblastoma that tends to affect patients at a young age, were investigated by immunohistochemical analysis and focused molecular genetic studies including array-based comparative genomic hybridization. All 5 cases had supratentorial tumors that immunohistochemical analysis revealed to be robustly positive for epithelial membrane antigen, vimentin, p53, and PDGFRα (platelet-derived growth factor receptor, alpha polypeptide) but only focally positive for glial fibrillary acidic protein. Although complete retention of SMARCB1 (INI1) was observed in all 5 cases, epidermal growth factor receptor (EGFR) amplification, PTEN (phosphatase and tensin homolog) loss, homozygous deletion of cyclin-dependent kinase inhibitor 2A, 1p/19q codeletion, and isocitrate dehydrogenase 1 R132/IDH2 R172 mutation were not observed in any case, although a high level of EGFR polysomy was detected in 1 recurrent tumor. Although c-MET (MET protein) expression was focal but robustly positive in 3 cases, met proto-oncogene (MET) fluorescence in situ hybridization revealed low polysomy but not MET amplification. MGMT (O-6-methylguanine-DNA methyl-40 transferase) methylation-specific polymerase chain reaction revealed MGMT methylation in only 1 case. Furthermore, array-based comparative genomic hybridization revealed gain of chromosome 7 and loss of 1p, 6, 8p, 11, 13q, and 18q but no deletion of chromosome 22. In contrast to the classical subtype of primary glioblastoma, the cases studied here were characterized by the absence of EGFR amplification, PTEN loss, and 9p homozygous deletion and overexpression of p53, PDGFRα, and c-MET, suggesting that they can be classified as the proneural or mesenchymal subtype of glioblastoma and benefit from intensive therapy that includes temozolomide.
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea, 110-799.
Sun-Ju
SJ
Byeon
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea, 110-799.
Hwa Jin
HJ
Cho
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea, 110-799.
Hae Woon
HW
Baek
Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Chul-Kee
CK
Park
Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Seung-Hong
SH
Choi
Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea, 120-749.
Se-Hoon
SH
Kim
Department of Pathology, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea, 420-767.
Hee Kyung
HK
Kim
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea, 110-799; Neuroscience Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: shparknp@snu.ac.kr.
Sung-Hye
SH
Park
D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D003582:Cytogenetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003937:Diagnosis, Differential; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics; D000090063:Proto-Oncogene Mas; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; C512478:EGFR protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase
Comparative genomic hybridization; Copy number variation; Glioblastoma; INI1 gene; Molecular genetics; Rhabdoid glioblastoma