Whole Genome Analysis From Microdissected Tissue Revealed Adult Supratentorial Grade II-III Gliomas Are Divided Into Clinically Relevant Subgroups by Genetic Profile

• Published in: Neurosurgery Vol. 69; no. 2; pp. 376 - 390
• Main Authors: Hirose, Yuichi, Sasaki, Hikaru, Miwa, Tomoru, Ohba, Shigeo, Ikeda, Eiji, Abe, Masato, Ikeda, Shunya, Kobayashi, Mia, Kawase, Tsukasa, Hasegawa, Mitsuhiro, Yoshida, Kazunari
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Oxford University Press 01-08-2011; Lippincott Williams & Wilkins; Wolters Kluwer Health, Inc
• Subjects: Biological and medical sciences; Brain Neoplasms - classification; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Comparative Genomic Hybridization; Disease-Free Survival; Gene Expression Profiling; Genome-Wide Association Study; Glioma; Glioma - classification; Glioma - genetics; Glioma - pathology; Humans; Kaplan-Meier Estimate; Medical sciences; Microdissection; Neoplasm Grading; Neurosurgery; Pilot Projects; Polymerase Chain Reaction; Proportional Hazards Models; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tumors; Comparative genomic hybridization; Tissue microdissection; Diffuse astrocytoma; Nervous system diseases; Glioma; Surgery; Central nervous system disease; Tumor; Genome; Astrocytoma
• ISSN: 0148-396X; 1524-4040
• DOI: 10.1227/NEU.0b013e318212bcd8

Abstract
BACKGROUND:
Gliomas are classified into pathologically defined subgroups. However, the tumors in the same entity could show varied 'clinical courses. Recently, various studies revealed that genetic analyses of gliomas can provide clinically relevant information.
OBJECTIVE:
To investigate the correlation between genetic characterization and clinical information of adult supratentorial grade II-III gliomas to establish a genetic classification of these tumors.
METHODS:
We analyzed the genetic profile of tumor samples microdissected from formalin-fixed archival tissue sections based on the defined selection criteria of tumor region using a comparative genomic hybridization method. We collected genetic and clinical data from 140 adult supratentorial gliomas of World Health Organization grade II-III and classified the tumors analyzed into subgroups according to chromosomal copy number aberrations. The relationship between histologic or genetic subclassification and clinical features was analyzed.
RESULTS:
The tumors were classified into subgroups based on the genetic profiles. Tumors with +7q and those with −1p/19q showed long progression-free survival, and loss of 10q in association with gain of 7p (+7/−10q) appeared to predict poor outcome. Most tumors with histologic diagnosis of glioblastoma showed +7/−10q; however, World Health Organization grade II-III gliomas contained a variety of genetic subgroups that correlated well with the clinical course, and this might explain why these tumors do not respond uniformly to therapies.
CONCLUSION:
Our pilot study suggests that care must be taken in clinical studies of these tumors because, unlike glioblastoma, grade II-III tumors may contain genetically distinct subgroups with different sensitivity to the therapies.