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High frequency of the X-chromosome inactivation in young female patients with high-grade glioma

Gang Li15, Zhiguo Zhang1, Tianbo Jin2, Hongjuan Liang1, Yanyang Tu3, Li Gong4, Zhongping Chen5* and Guodong Gao1*

Author affiliations

1 Department of Neurosurgery, Tangdu hospital, the Fourth Military Medical University, 710038 Xi’an, China

2 National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, 710069 Xi’an, China

3 Department of Clinical Experimental Surgery, Tangdu hospital, the Fourth Military Medical University, 710038 Xi’an, China

4 Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, 710038 Xi’an, China

5 Department of Neurosurgery, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, 510060 Guangzhou China

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Citation and License

Diagnostic Pathology 2013, 8:101  doi:10.1186/1746-1596-8-101

Published: 19 June 2013

Abstract

Background

Gliomas are common tumors and high-grade ones account for 62% of primary malignant brain tumors. Though current evidence have suggested that inherited risks play a role in glioma susceptibility, it was conveyed that glioma was such a complex disease, and the direct genetic contribution to glioma risk factors and its relation to other factors should be discussed more deeply. X-chromosome inactivation (XCI) is the mechanism by which gene dosage equivalence is achieved between female mammals with two X chromosomes and male mammals with a single X chromosome. As skewed XCI has been linked to development of some solid tumors, including ovarian, breast, and pulmonary and esophageal carcinomas, it is challenging to elucidate the relation of skewed XCI to high-grade gliomas development.

Objective

The present study aimed to determine the general concordance between XCI pattern in blood cells and brain tissues, and SXCI frequencies in female patients with high-grade glioma compared to healthy controls.

Methods

1,103 Chinese females without a detectable tumor and 173 female high-grade glioma patients, were detected in the study. Normal brain tissues surrounding the lesions in gliomas were obtained from 49 patients among the 173 ones, with the microdissection using a laser microdissection microscope Genomic DNA was extracted from the peripheral blood cells and the normal brain tissues from the subjects. Exon 1 of androgen receptor (AR) gene was amplified, and its products of different alleles were resolved on denaturing polyacrylamide gels and visualized after silver staining. The corrected ratios (CR) of the products before and after HpaII digestion were calculated.

Results

Occurrence of SXCI was detected in both the patients and controls at similar frequencies. However, the phenomenon, as defined as CR ≥ 3, was more frequent in the patients aging ≤40 (23.6%) compared to the corresponding reference group (5.1%, P <0.0001). When CR ≥ 10 was adopted, the frequencies were 5.5% and 1.6%, respectively. Their difference did not attain statistical significance (P = 0.10). When detected, both blood cells and brain tissue were compared after determination of a high concordance of XCI between blood cells and brain tissue collected from the same individuals (n = 48, r =0.57, P <0.01).

Conclusions

The data from the current study demonstrated that SXCI may be a predisposing factor for development of high-grade glioma in young female patients and further study will verify its suitability as a biomarker to assess susceptibility of young female patients to high-grade glioma.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1935066233982578 webcite

Keywords:
Skewed X-chromosome inactivation; Androgen receptor gene; Glioma; High-grade; Cancer predisposition; Laser microdissection