High-resolution array-based comparative genomic hybridization of medulloblastomas and supratentorial primitive neuroectodermal tumors

Medulloblastomas and supratentorial primitive neuroectodermal tumors are aggressive childhood tumors. We report our findings using array comparative genomic hybridization (CGH) on a whole-genome BAC/PAC/cosmid array with a median clone separation of 0.97 Mb to study 34 medulloblastomas and 7 supratentorial primitive neuroectodermal tumors. Array CGH allowed identification and mapping of numerous novel, small regions of copy number change to genomic sequence in addition to the large regions already known from previous studies. Novel amplifications were identified, some encompassing oncogenes MYCL1, PDGFRA, KIT, and MYB not previously reported to show amplification in these tumors. In addition, one supratentorial primitive neuroectodermal tumor had lost both copies of the tumor-suppressor genes CDKN2A and CDKN2B. Ten medulloblastomas had findings suggestive of isochromosome 17q. In contrast to previous reports using conventional CGH, array CGH identified 3 distinct breakpoints in these cases: Ch 17: 17940393-19251679 (17p11.2, n = 6), Ch 17: 20111990-23308272 (17p11.2-17q11.2, n = 4), and Ch 17: 38425359-39091575 (17q21.31, n = 1). Significant differences were found in the patterns of copy number change between medulloblastomas and supratentorial primitive neuroectodermal tumors, providing further evidence that these tumors are genetically distinct despite their morphologic and behavioral similarities.     

Chromosome 14q11.2‐q21.1 duplication: a rare cause of West syndrome

Proximal duplication of chromosome 14q, including the FOXG1 gene located on 14q12, is a rare condition characterised by developmental delay, dysmorphic craniofacial features, epilepsy, and severe speech delay. Here, we report a patient with West syndrome whose chromosome analysis revealed 14q11.2‐21.1 duplication. The patient was admitted due to infantile epileptic spasms at eight months of age, motor developmental delay, and dysmorphic features. Chromosome and array‐CGH analysis revealed de novo 14q11.2‐21.1 duplication, spanning ～20 Mb (minimal interval chr14:20203610_40396835). The patient was followed up to 13 years of age, and at the last examination was shown to have severe speech delay, seizures, and continuous spike‐and‐wave activity on EEG. The possibility of this chromosomal abnormality should be kept in mind in patients with developmental delay, epilepsy, and hypsarrtyhmia, in the absence of any structural brain lesion or metabolic aetiology.     

Searching for migraine genes: exclusion of 290 cM out of the whole human genome

A linkage and association analysis was made on 14 Italian families with recurrent migraine. We analyzed five chromosomal regions surrounding the candidate genes 5HT_1D (1p36.3–34.3), 5HT_1B (6q13), 5HT_2A (13q14–21), 5HT transporter (17q11.2–12), CACNLB1 (17q11.2–22) and FHM (19p13), using 29 DNA polymorphic markers. All two-point lod scores were negative, and the x2 sib-pair analyses were not significant, thus indicating the probable exclusion of these regions as sites of migraine genes in our population.This work was supported by MURST (40%) and CNR grant 2785 e 96.03122.CT04     

External Validation of the PHASES Score in Patients with Multiple Intracranial Aneurysms

ObjectivesThis study sought to assess whether the Population, Hypertension, Age, Size, Earlier Subarachnoid Hemorrhage, Site (PHASES) score can do risk stratification of patients with multiple aneurysms (MIAs).Material and MethodsPatients between January 1, 2016 and January 1, 2019 were recruited retrospectively. The PHASES score was applied to assess the theoretical risk of IA rupture. For patients-level analyses, four modes of the application of the score were used: largest IA PHASES score, highest PHASES score, sum PHASES score, and mean PHASES score.ResultsA total of 701 patients with 1673 IAs were included in this study. At aneurysm-level analysis, the average PHASES score was 3.0 ± 3.0 points, with 2.8 ± 3.0 points and 4.1 ± 2.9 points in the unruptured and ruptured groups, respectively (p < 0.001). At the patient-level analysis, for the largest IA PHASES score, the areas under the curves (AUC) was 0.572. The discrimination performance of the largest IA PHASES score decreases as IA number increases, with AUCs were 0.597, 0.518, and 0.450 in the 2 IAs, 3 IAs and, 4 or more IAs subgroups, respectively. For highest PHASES score, sum PHASES score, and mean PHASES score, the AUCs were 0.577, 0.599, and 0.619, respectively.ConclusionsIn this study, PHASES score only serve as a weak tool in decision-making settings for MIAs patients; as such, more accurate models should be developed for MIAs patients and the cumulative effect of MIA may should be considered.     

Spatial variability of genomic aberrations in a large glioblastoma resection specimen

In the present study, the distribution of genetic aberrations in a glioblastoma resection specimen of unusually large size (9x8x2 cm) was investigated using comparative genomic hybridization (CGH). CGH was performed on 20 samples taken from the specimen, and the genetic aberrations found were compared with the regional histology. The samples were histopathologically graded according to WHO criteria, and a division in high- and low-grade areas and infiltration rims was made. In high-grade areas, low-grade areas as well as infiltration rims, gains on 10p11.2-pter (14/20), 11q12-q22 (6/20) and losses on 4q13-qter (9/20), 10q22-qter (8/20), 11p14-pter (5/20), 13q12-qter (7/20) were revealed. Gains on 1q21-32 (2/4) and losses on 7p21-pter (3/4) were exclusively found in the high-grade areas. In the low-grade tumor samples and in the infiltration rim, gains on 16p11.2-pter (6/16), 17p11.2-pter (6/16), 17q11.2-qter (5/16), 20q11.2-q13 (3/16) and deletions on 5q31-qter (4/16) were detected. Gains on 7q21-qter (8/11) and 8q11.2-qter (6/11), and loss of chromosome 9 (4/11) and the Y-chromosome (4/11) were found in the high-grade and low-grade samples, not in the infiltration rims. The finding of a set of identical chromosomal aberrations throughout the resection specimen, most of which have been previously reported in gliomas, confirms a mechanism of clonal tumor proliferation operative in gliomas. The previously unreported genetic alterations which were predominantly traced in the tumor rims, might reflect either selection for properties related to infiltrating behavior, or genomic instability of subclones. The findings illustrate the importance of searching for high-grade genetic aberrations in low-grade tumor samples taken from cases in which sampling error is suspected.     

Biphasic malignant meningioma: a comparative genomic hybridization study

To ascertain if a carcinoma-like component within a fibroblastic meningioma represented a metastatic carcinoma to a meningioma or malignant progression, we employed traditional immunohistochemical methods as well as comparative genomic hybridization (CGH) which compares chromosomal alterations. Vimentin and epithelial membrane antigen were strongly immunoreactive in both the fibroblastic and carcinoma-like components. The CGH profile in both components had similar chromosomal alterations, including losses of 1p, 14, 16p13-->p10 and 22. However, the CGH profiles from the fibroblastic component showed losses of 4p, 10q23-->q24 and 18, along with gains of 1q, 6q25-->qter and 13q32-->qter. The profile of the carcinoma-like component showed losses of chromosome 4, in addition to gains of 3p12-->q13.11, 5q14.3-->q23.2, 6pter-->p23, and 13q14.2-->qter. CGH analysis of a biphasic malignant meningioma confirmed that the disparate histologic components were genetically related and likely derivative from a common precursor, demonstrating genetic instability and clonal expansion. Furthermore, CGH showed that the histologically appearing low-grade fibroblastic component had not solely the characteristic alterations of a benign meningioma but had already progressed to an atypical meningioma.     

Chromosomal imbalances detected by comparative genomic hybridisation in atypical teratoid/rhabdoid tumours

Introduction Atypical teratoid/rhabdoid tumours (AT/RT) are highly malignant embryonal tumours of the brain composed of rhabdoid cells. Inactivating mutations of the hSNF5/INI-1 gene located in the chromosomal region 22q11.2 are regarded as a crucial step in their molecular pathogenesis. Apart from monosomy or deletions of chromosome 22 not much data exists on additional chromosomal aberrations.Methods We investigated seven primary AT/RT by comparative genomic hybridisation (CGH) and found DNA copy number changes in each case.Results These consisted of loss of 22q in 7 out of 7 (100%) and loss of 19 in 3 out of 7 (43%) patients. In 4/7 AT/RT (57%), loss of chromosome 22q was the sole aberration whereas one patient showed additional losses of 16p, 17p and 20q.Conclusions Our CGH data suggest that apart from monosomy 22 additional genetic pathways may seem feasible for a subset of AT/RT that is yet to be defined. Furthermore, this study also emphasises the potential practical value of loss of chromosome 22 as a diagnostic marker for AT/RT.     

颅内动脉瘤形态参数同破裂风险相关性的对比研究

目的本研究旨在评估颅内动脉瘤的几何形态参数与其破裂风险之间的关系,以筛选出关键的动脉瘤破裂风险预测因子。方法回顾性研究2009年3月至2011年4月西安交通大学第一附属院神经外科收治的44例颅内动脉瘤病例,共52枚侧壁动脉瘤,其中36枚破裂动脉瘤,16枚未破裂动脉瘤。采用三维头颅CTA获得动脉瘤三维影像,测定动脉瘤大小及纵横比等二维形态参数及动脉瘤入射夹角等三维形态参数。运用t检验、卡方检验及Pearson相关进行数据分析。结果破裂动脉瘤组与未破裂动脉瘤组相比,入射夹角、动脉瘤长径和瘤高具有明显统计学差异(P<0.05)。破裂组动脉瘤的入射夹角明显大于未破裂组。同样,破裂组动脉瘤较未破裂组具有更长的瘤长径和瘤高。Pearson相关分析示动脉瘤入射夹角与动脉瘤破裂风险最为相关。结论动脉瘤入射夹角与动脉瘤破裂风险密切相关,可作为预测颅内未破裂动脉瘤破裂风险的重要评估因子之一。     

Multidimensional predicting model of intracranial aneurysm stability with backpropagation neural network: a preliminary study

Objectives

The stability of intracranial aneurysms (IAs) may involve in multidimensional factors. Backpropagation (BP) neural network could be adopted to support clinical work. This preliminary study aimed to delve into the feasibility of BP neural network in assessing the risk of IA rupture/growth and to prove the advantage of multidimensional model over single/double-dimensional model.

Methods

Thirty-six IA patients were recruited from a prospective registration study (ChiCTR1900024547). All patients were followed up until aneurysm ruptured/grew or 36 months after being diagnosed with the IAs. The multidimensional data regarding clinical, morphological, and hemodynamic characteristics were acquired. Hemodynamic analyses were conducted with patient-specific models. Based on these characteristics, seven models were built with BP neural network (the ratio of training set to validation set as 8:1). The area under curves (AUC) was calculated for subsequent comparison.

Results

Forty-five characteristics were determined from 36 patients with 37 IAs. In the models based on the single dimension of IA characteristics, only morphological characteristics exhibited high performance in assessing 3-year IA stability (AUC = 0.703, P = 0.035). Among the models integrating two dimensions of IA characteristics, clinical-morphological (AUC = 0.731, P = 0.016), clinical-hemodynamic (AUC = 0.702, P = 0.036), and morphological-hemodynamic (AUC = 0.785, P = 0.003) models were capable of assessing the risk of 3-year IA rupture/growth. Moreover, the models including all three dimensions exhibited the maximum predicting significance (AUC = 0.811, P = 0.001).

Conclusion

The present preliminary study reported that BP neural network might support assessing the 3-year stability of IAs. Models based on multidimensional characteristics could improve the assessment accuracy for IA rupture/growth.

     

Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization.

In contrast to astrocytic tumors, approximately two thirds of anaplastic oligodendrogliomas are reported to be chemosensitive. Relatively little is known about the genetic aberrations in oligodendroglial tumors (OTs). In order to elucidate oligodendroglial oncogenesis and to find specific genetic aberrations that may have prognostic and therapeutic implications, we performed comparative genomic hybridization (CGH) to detect chromosomal copy number changes in 17 low-grade OTs (LG-OTs) and 12 high-grade OTs (HG-OTs) lacking a prominent astrocytic component. Loss of chromosome 1p (79%) and 19q (76%) were most frequently detected by CGH, all LG-OTs and 50% of the HG-OTs contained -1p (including 1p36-32), -19q (including 19q13.3), or both, and the rest of the HG-OTs showed +7, -10, or both. Since losses of 1p36-32 and 19q13.3 were mutually exclusive with +7 or -10, the HG-OTs could be divided in -1p/-19q and +7/-10 tumors. While the -1p/-19q tumors can be considered as pure anaplastic oligodendrogliomas, the +7/-10 tumors may rather be glioblastomas with prominent oligodendroglial differentiation. We conclude that CGH is a powerful tool to assist in the identification of 2 major subgroups of HG-OTs with prognostic and possibly therapeutic relevance.     

Genome-Wide Association Study of the Relationship Between Matrix Metalloproteinases and Intracranial Aneurysms

Background and PurposeMatrix metalloproteinases (MMPs) are expected to play an important role in extracellular matrix (ECM) remodeling in response to hemodynamic stress. We investigated the association between MMPs and intracranial aneurysms (IAs) via a genome-wide association study (GWAS) of IAs.MethodsA GWAS data set of 250 IAs and 294 controls was used to analyze the genetic link between MMPs and IAs via single-nucleotide polymorphisms (SNPs), MMP gene families, and in silico functional analyses of gene ontology (GO) enrichment and protein–protein interaction (PPI).ResultsForty-eight SNPs and 1 indel out of 342 markers of MMP genes were related to IAs. The rs2425024 SNP located on MMP24 was the most strongly associated with IAs (OR=0.43, CI=0.30–0.61, p=2.4×10^-6), suggesting a protective effect. The 16938619 SNP of MMP26 significantly increased the risk of an IA (OR=3.12, 95% CI=1.76–5.50, p=8.85×10^-5). Five MMP genes (MMP24, MMP13, MMP2, MMP17, and MMP1) increased the susceptibility to an IA. MMP24 was the gene most closely related to IAs (p=7.96×10^-7). GO analysis showed that collagen catabolism was the most-enhanced biological process. Further, metalloendopeptidase activity and ECM were predominantly detected in the cellular component and molecular function, respectively. PPI provided evidence that MMP2, TIMP2 (tissue inhibitor of metalloproteinase 2), and TIMP3 genes constitute a network for predicting IA formation.ConclusionsThe present results provide comprehensive insight into the occurrence of IAs associated with MMPs.     

Methylation Status of the O6-Methylguanine-Deoxyribonucleic Acid Methyltransferase Gene Promoter in World Health Organization Grade III Gliomas

Objective

We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter in World Health Organization (WHO) grade III gliomas in association with other molecular markers to evaluate their prevalence.

Methods

The samples of a total of 36 newly WHO grade III glioma patients including 19 anaplastic oligodendrogliomas (AO), 7 anaplastic oligoastrocytomas (AOA), and 10 anaplastic astrocytomas (AA) were analyzed. The methylation status of the MGMT gene promoter was confirmed by methylation-specific polymerase chain reaction. The 1p/19q chromosomal deletion status and EGFR amplification were assessed by Fluorescence In-Situ Hybridization. MGMT, EGFR, EGFRvIII, and p53 expression were analyzed by immunohistochemical staining.

Results

The MGMT gene promoter was methylated in 32 (88.9%) and unmethylated in 4 (11.2%). Among them, all of the AO and AOA had methylated MGMT gene promoter without exception. Significant associations between MGMT gene promoter hypermethylation and 1p/19q deletion was observed (p = 0.003). Other molecular markers failed to show significant associations between MGMT gene promoter statuses.

Conclusion

There was extensive epigenetic silencing of MGMT gene in high grade gliomas with oligodendroglial component. Together with frequent 1p/19q co-deletion in oligodendroglial tumors, this may add plausible explanations supporting the relative favorable prognosis in oligodendroglial tumors compared with pure astrocytic tumors.     

Altered DNA copy number in patients with different seizure disorder type: by array-CGH

Epilepsy is one of the most common but genetically complex neurological disorders in children. Previous studies have showed that chromosomal abnormalities confer susceptibility to epilepsy. To identify new chromosomal abnormalities associated with epilepsy, DNA samples from patients with idiopathic generalized epilepsy (IGE), partial epilepsy (PE), and febrile seizures (FS) were analyzed using array comparative genome hybridization technique (array-CGH). Genomic aberrations were detected throughout whole chromosome. The most frequently altered loci were gains noted in: 1p (60%), 5p (55%), 8q (55%), 10q (55%), and losses in 7q (55%). The most frequent chromosomal aberrations for each seizure type were: IGE-1p (60%), 5p (55%), and 10q (55%), PE-11p (45%), 21q (45%) and FS-8q (55%), and losses in 7q (55%). To validate the array-CGH results, real time PCR was performed for several genes (EPM2AIP1, OSM, AFP, CYP19A1, SLC6A13, and COL6A2). The results from the real time PCR were consistent with those from the array-CGH. Therefore, we found that the three types of seizures disorder studied have different chromosomal aberrations. These results might be used for further investigation of the pathogenesis of epilepsy.     

Intracranial infectious aneurysm: presentation, management and outcome

BACKGROUND: Intracranial infectious aneurysms (IA) are infrequent, but can be fatal. OBJECTIVES: To compare the clinical profile of IAs associated with intravascular/systemic infection like infective endocarditis with that associated with local infections like meningitis, orbital cellulitis and cavernous sinus thrombosis. METHODS: We analysed all cases of IA, treated in this Institute from 1976 to 2003, in order to identify prognostic factors. RESULTS: There were 25 persons (mean age 24.8+/-17.3 years, males 17) with 29 IA (carotid circulation 19, vertebrobasilar circulation 10). Headache (83%) and fever (67%) were the most common presenting symptoms. In contrast to noninfectious aneurysms, intracerebral haemorrhage (60%) and focal signs were more common than subarachnoid haemorrhage (7%) with IA. Sources of infection were cardiac (10), meningitis (12), orbital cellulitis (2) or uncertain (1). Infective agents included bacteria (18), fungi (4), and tubercle bacilli (3). Fifteen IA were distal and 14 were proximal. IAs associated with meningitis were proximal (75%) while those associated with cardiac diseases preferentially involved carotid territory and were distal (p=0.013). The overall mortality was 32%. Survivors were younger than those who expired (p=0.015). Of the sixteen patients treated medically, seven recovered (44%), others (56%) had treatment failure (three died and six required surgery later). Another five patients underwent early surgery (one died). Mortality of IA was significantly higher with meningitis, fungal aetiology and vertebrobasilar location. CONCLUSIONS: IAs associated with local infections like meningitis had different clinical profile as compared to IAs associated with intravascular/systemic infections like infective endocarditis.     

Benign infantile seizures followed by autistic regression in a boy with 16p11.2 deletion

Benign infantile seizures (BIS) are usually a self‐limiting condition, which may be associated with heterozygous mutations in the PRRT2 gene at chromosome 16p11.2. Here, we report a boy with a deletion in 16p11.2, presenting with BIS and typical neurodevelopment in the first year of life, unexpectedly followed by severe autistic regression. 16p11.2 deletions are typically associated with intellectual disability, autism, and language disorders, and only rarely with BIS. This clinical report shows that the neurodevelopmental prognosis in BIS patients may not always be benign, and suggests that array CGH screening should be considered for affected infants in order to rule out deletions at 16p11.2 and long‐term clinical follow‐up.     

Clinically detectable copy number variations in a Canadian catchment population of schizophrenia

Copy number variation (CNV) is a highly topical area of research in schizophrenia, but the clinical relevance is uncertain and the translation to clinical practice is under-studied. There is a paucity of research involving truly community-based samples of schizophrenia and widely available laboratory techniques. Our objective was to determine the prevalence of clinically detectable CNVs in a community sample of schizophrenia, while mimicking typical clinical practice conditions. We used a brief clinical screening protocol for developmental features in adults with schizophrenia for identifying individuals with 22q11.2 deletions and karyotypically detectable chromosomal anomalies in 204 consecutive patients with schizophrenia from a single Canadian catchment area. Twenty-seven (13.2%) subjects met clinical criteria for a possible syndrome, and 26 of these individuals received clinical genetic testing. Five of these, representing 2.5% of the total sample (95% CI: 0.3%-4.6%), including two of ten patients with mental retardation, had clinically detectable anomalies: two 22q11.2 deletions (1.0%), one 47, XYY, and two other novel CNVs - an 8p23.3-p23.1 deletion and a de novo 19p13.3-p13.2 duplication. The results support the utility of screening and genetic testing to identify genetic syndromes in adults with schizophrenia in clinical practice. Identifying large, rare CNVs (particularly 22q11.2 deletions) can lead to significant changes in management, follow-up, and genetic counselling that are helpful to the patient, family, and clinicians.     

Developmental changes in multivariate neuroanatomical patterns that predict risk for psychosis in 22q11.2 deletion syndrome

The primary objective of the current prospective study was to examine developmental patterns of voxel-by-voxel gray and white matter volumes (GMV, WMV, respectively) that would predict psychosis in adolescents with 22q11.2 deletion syndrome (22q11.2DS), the most common known genetic risk factor for schizophrenia. We performed a longitudinal voxel-based morphometry analysis using structural T1 MRI scans from 19 individuals with 22q11.2DS and 18 typically developing individuals. In 22q11.2DS, univariate analysis showed that greater reduction in left dorsal prefrontal cortical (dPFC) GMV over time predicted greater psychotic symptoms at Time2. This dPFC region also showed significantly reduced volumes in 22q11.2DS compared to typically developing individuals at Time1 and 2, greater reduction over time in 22q11.2DS COMT^Met compared to COMT^Val, and greater reduction in those with greater decline in verbal IQ over time. Leave-one-out Multivariate pattern analysis results (MVPA) on the other hand, showed that patterns of GM and WM morphometric changes over time in regions including but not limited to the dPFC predicted risk for psychotic symptoms (94.7-100% accuracy) significantly better than using univariate analysis (63.1%). Additional predictive brain regions included medial PFC and dorsal cingulum. This longitudinal prospective study shows novel evidence of morphometric spatial patterns predicting the development of psychotic symptoms in 22q11.2DS, and further elucidates the abnormal maturational processes in 22q11.2DS. The use of neuroimaging using MVPA may hold promise to predict outcome in a variety of neuropsychiatric disorders.     

The genetics of reading disability

Genetic factors contribute substantially to the development of reading disability (RD). Family linkage studies have implicated many chromosomal regions containing RD susceptibility genes, of which putative loci at 1p34–p36 (DYX8), 2p (DYX3), 6p21.3 (DYX2), and 15q21 (DYX1) have been frequently replicated, whereas those at 3p12–q12 (DYX5), 6q13–q16 (DYX4), 11p15 (DYX7), 18p11 (DYX6), and Xq27 (DYX9) have less evidence. Association studies of positional candidate genes have implicated DCDC2 and KIAA0319 in DYX2, as well as C2ORF3 and MRPL19 (DYX3), whereas DYX1C1/EKN1 (DYX1) and ROBO1 (DYX5) were found to be disrupted by rare translocation breakpoints in reading-disabled individuals. Four of the candidate genes (DYX1C1, KIAA0319, DCDC2, and ROBO1) appear to function in neuronal migration and guidance, suggesting the importance of early neurodevelopmental processes in RD. Future studies to help us understand the function of these and other RD candidate genes promise to yield enormous insight into the neurobiologic mechanisms underlying the pathophysiology of this disorder.     

少突胶质细胞起源肿瘤染色体DNA失衡的比较基因组杂交研究

目的 探讨少突胶质细胞起源肿瘤基因组DNA失衡及其与病理分级的关系.方法 用比较基因组杂交技术检测了33例少突胶质细胞起源肿瘤石蜡包埋组织,分析其全基因组DNA失衡状况.结果 少突胶质细胞瘤(ODG)及间变性少突胶质细胞瘤(AODG)的基因组DNA失衡检出率分别为100%(16/16)和88%(15/17),共发现24个有DNA获得和24个有DNA丢失的染色体区带.其中,-19q、-1p/-19q联合性缺失检出率在ODG组明显高于AODG组(P<0.05),+7p检出率在AODG组明显高于ODG组(P<0.05).在22对常染色体及X染色体中,+1q、+7P、+8P、+8q、+9q、+18p、+18q、+20p及-1p、-19q、-Xq出现频率较高.+2q、+4p、+4q、+6p、+10p、+15q、+20q、+22q仅见ODG组,+11q、+12p、+Xp仅见于AODG组.而-3p、-5q、-8p、-12p、-12q、-15q、-19p、-20q、-XP仅见ODG组,-2q、-4p、-4q、-5p、-6q、-7p、-11q、-14q仅见于AODG组.结论 ODG和AODG均有各自特征性的染色体基因组DNA失衡谱;-1p/-19q是评价国人该类肿瘤生物学行为的重要参考指标,对治疗敏感性及患者预后判断有重要的指导意义;+7p和-19q对评估国人该类肿瘤的生物学行为和患者预后有一定参考价值.

Abstract：

Objective To investigate the relationship between genomic DNA imbalance in oligodendroglial tumors and its different classification.Method 16 oligodendrogliomas and 17 anaplastic oligodendrogliomas were investigated by comparative genomic hybridization on Paraffin-Embedded tissue samples, and the chromosomal genomic DNA imbalances were analyzed.Results Chromosome DNA imbalance rates in oligodendrogliomas and anaplastic oligodendrogliomas are 100% and 88% respectively,and chromosomal regions of 24 gains and 24 losses were found in these tumors.19q loss and 1p/19q loss are frequent in oligodendroglioma.The gain of 7p happened predominantly in anaplastic oligodendroglioma, and their differences were significant(P < 0.05 ).+ 1q, + 7p, + 8p, + 8q, + 9q, + 18p, + 18q, + 20p and-1p,-19q,-Xq are frequently occurred in oligodendroglial tumors.+2q, +4p, +4q, +6p, + 10p,+ 15q, + 20q and + 22q are only identified in oligodendroglioma, + 11q, + 12p and + Xp are only identified in anaplastic oligodendroglioma.-3p,-5q,-8p,-12p,-12q,-15q,-19p,-20q and-Xp are only identified in oligodendroglioma, and-2q,-4p,-4q,-5p,-6q,-7p,-11q and-14q are only identified in anaplastic oligodendroglioma.Conclusions The characteristic imbalance spectrum of oligodendroglial tumors is the molecular genetic base to determine their histological phenotype and grade.-1p/-19q are also the important molecular genetic markers to estimate biological behavior,chemotherapy sensitivity of these tumors and patients' prognosis.+7p and-19q may be useful to evaluate the biological behavior of these tumors and patients' prognosis.