TERT promoter mutated WHO grades II and III gliomas are located preferentially in the frontal lobe and avoid the midline.

Abstract

The promoter region of telomerase reverse transcriptase (TERTp) and isocitrate dehydrogenase (IDH) have been regarded as biomarkers with distinct clinical and phenotypic features. Investigated the possible correlations between tumor location and genetic alterations would enhance our understanding of gliomagenesis and heterogeneity of glioma. We examined mutations of TERTp and IDH by direct sequencing and fluorescence in-situ hybridization in a cohort of 225 grades II and III diffuse gliomas. Correlation analysis between molecular markers and tumor locations was performed by Chi-square tests/Fisher's exact test and multivariate logistic regression analysis. We found gliomas in frontal lobe showed higher frequency of TERTp mutation (P=0.0337) and simultaneously mutations of IDH and TERTp (IDH (mut)-TERTp(mut)) (P=0.0281) than frequency of biomarkers mutation of tumors in no-Frontal lobes, while lower frequency of TERTp mutation (P<0.0001) and simultaneously wild type of IDH and TERTp (IDH (wt)-TERTp(wt)) (P<0.0001) in midline than no-midline lobes. Logistic regression analysis indicated that locations of tumors associated with TERTp mutation (OR=0.540, 95% CI 0.324-0.900, P=0.018) and status of combinations of IDH and TERTp (IDH (mut)-TERTp (mut) vs. IDH (wt)-TERTp (wt) OR=0.162, 95% CI 0.075-0.350, P<0.001). In conclusion, grades II and III gliomas harboring TERTp mutation were located preferentially in the frontal lobe and rarely in midline. Association of IDH-TERTp status and tumor location suggests their potential values in molecular classification of grades II and III gliomas.

• Authors: Ze-Lin Sun, Aden Ka-Yin Chan, Ling-Chao Chen, Chao Tang, Zhen-Yu Zhang, Xiao-Jie Ding, Yang Wang, Chong-Ran Sun, Ho-Keung Ng, Yu Yao, Liang-Fu Zhou
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 9 Pg. 11485-94 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26617880 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isocitrate Dehydrogenase
• TERT protein, human
• Telomerase

Topics

• Adult
• Brain Neoplasms (genetics, pathology)
• DNA Mutational Analysis
• Female
• Frontal Lobe (pathology)
• Glioma (genetics, pathology)
• Humans
• In Situ Hybridization, Fluorescence
• Isocitrate Dehydrogenase (genetics)
• Male
• Middle Aged
• Mutation
• Neoplasm Grading
• Promoter Regions, Genetic (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Telomerase (genetics)
• World Health Organization