Study On Comparative Genomic Hybridization Of Chromosomal DNA Imbalance In Ependymomas

Objective:To detect whether there were genomic DNA gain and/or loss in all chromosomes in ependymomas(EDMs) and determine the distribution of DNA imbalance regions in chromosomes,in order to investigate the relationship between genomic DNA imbalances of all chromosomes in EDMs,and their histological types,grades and localizations as well as patients' gender and age.The research aimecd to identify the useful molecular genetics markers which were helpful to pathological diagnosis,differentiation,and evaluations of biological behaviour and prognosis.The molecular genetics clues were also provided for finally understand the development and progression of these tumors.Methods:A total of 22 archived paraffin-embeded tissue samples of EDMs were obtained at the neuropathology department of Tianjin medical university general hospital from 2000 to 2008.All of the 22 cases include 3 myxopapillary EDMs(MPE,WHO gradeⅠ),7 cellular EDMs(CE,WHO gradeⅡ),6 tanycytic EDMs(TE,WHO gradeⅡ) and 6 anaplastic EDMs(AE,WHO gradeⅢ).Their pathological diagnosis was confirmed again.Pan-genomic DNA of all the tumors was extracted from formalin-fixed and paraffin-embedded tissue section.The reference Pan-genomic DNA was extracted from leukocytes of normal male donors. Both of the DNAs were labeled by nick translation technology.The gains and losses of chromosomal genomic DNA and their distribution characters in 22 EDMs were analyzed using comparative genomic hybridization.Results:The gains and losses were found in 21(95.5%) and 18(81.8%)of 22 EDMs respectively,and chromosomal regions of 26 gains and 19 losses were confirmed in these tumors.Both of the gain and loss regions of MPE(WHO gradeⅠ) were the most,and these of CE(WHO gradeⅡ) and TE(WHO gradeⅡ) were more than those of AE(WHO gradeⅢ).Some of the gain and loss regions only betided in one of MPE,CE,TE and AE,which made the every subtype show specific imbalance spectrum of genomic DNA.It was their common feature that MPE,CE and TE had often +7.+5 only occurred in MPE and CE as well as-22q just in CE and TE.AE oftenest appeared +1q,however,all of them did not have +5,+7,-4q, -19q and -22q which were frequent in MPE,CE and TE.The occurring frequency of any gain or loss region was not affected by patients' gender,and the sex differences were not significant(P＞0.05).+1q +7p and +9q happened predominantly in EDMs of onset age≤30 years,+7 and -22q predominantly in EDMs of onset age＞30 years, and their differences were significant(P＜0.05).+1q and +7p happened predominantly in intracranial EDMs,+7 was only detected in spinal ones and their differences were significant(P＜0.05～0.01).Conclusion The frequency of genomic DNA imbalance in EDMs decreases with their grade.The characteristic imbalance spectrum of above every subtype is the molecular genetic base to determine their histological phenotype and grade.+1q,+5, +7p,+7,-4q,+9q,-19q and -22q are the important molecular genetic markers to estimate biological behavior of these tumors and patients' prognosis.