No abstract

The role of epigenetics and significance of aberrant gene regulation in etiology of cancer is a well-established phenomenon. The hallmark of cancer epigenetics is aberrant DNA methylation consisting of global hypomethylation and regional hypermethylation of tumor suppressor genes (TSGs) by DNA methyltransferases (DNMTs). In mammals, DNA methylation is catalyzed by DNMTs encoded by DNMT1, DNMT3A, and DNMT3B. Interestingly, little is known about variation in the methylation status of epigenetic regulators themselves in gliomas. Here, we report significant overexpression of DNMT1 and DNMT3B. A study of the methylation status and histone modifications at the promoter region of DNA methyltransferase I (DNMT1) gene revealed an unmethylated DNA promoter, similar to that detected in normal brain tissues. However, a differential histone code with distinct euchromatin marks--AcH3, AcH4, and H3k4me2--was specifically detected in tumors, unlike in normal brain tissues, which were found predominantly enriched with heterochromatin marks such as H3K9me2 and H3K27me3. In contrast, a differential methylation pattern of DNMT3B gene promoter occurred in glioma tumors, wherein it was found hypomethylated. Transcriptional silencing by CpG island methylation is a prevalent mechanism for inactivation of TSGs. Inhibiting DNMTs by 5-azacytidine (DNMT inhibitor) treatment led to significant inhibition of expression of DNMT1 and DNMT3B and enhanced expression of TSGs such as PTEN and p21 analyzed in this study. Our studies have identified effects of increased presence of DNMTs on inhibition of tumor suppressors that are epigenetically silenced in gliomas, thereby leading to aberrant regulation of cell cycle progression and failure to maintain genomic stability.

Object This study is a retrospective analysis of 60 surgically treated patients with 64 peripheral nerve sheath tumors (PNSTs) at the second cervical (C-2) nerve root. The anatomical subtleties of these tumors and their implications for surgical strategy when compared with other spinal PNSTs and other tumors in the foramen magnum region are reviewed. Methods Sixty patients with C-2 PNSTs treated surgically in the Department of Neurosurgery at King Edward VII Memorial Hospital and Seth Gordhandas Sunderdas Medical College between 1992 and 2006 were studied. All patients underwent magnetic resonance imaging. Tumors were divided into 3 groups depending on their anatomical location identified during surgery. Those tumors located within or extending into the spinal dural tube were called Type A, those located within the dural tube of the C-2 ganglion were labeled as Type B, and tumors extending laterally into the paraspinal region were labeled as Type C. Follow-up durations ranged from 6 months to 15 years (mean 64 months). Results There were 38 male and 22 female patients in the study, who ranged in age from 6 to 62 years (mean 28 years). Nine patients had clinical features indicative of neurofibromatosis (NF). The mean duration of symptoms at the time of presentation was 27 months (range 4 days–5 years). Two patients had no specific symptoms related to the C-2 PNST, 6 patients had only local symptoms such as neck pain or stiffness, and 52 patients had symptoms of varying degrees of myelopathy. There were 5 solely Type A tumors, 7 Type A + B tumors, 31 Type B tumors, and 21 Type B + C tumors. All Type A, A + B, and B tumors were totally resected. Seven of 21 Type B + C tumors were partially resected, and the remainder were completely resected. All patients postoperatively reported varying improvement in their preoperative symptoms. Except for patients with NF who were disabled by other tumors, the rest of the patients resumed their normal life style. There have been no cases of symptomatic tumor recurrence. Conclusions The majority of PNSTs located at the C-2 level in these patients probably arose from the large C-2 ganglion and are limited within the dural confines or are interdural in location. In contrast to other spinal PNSTs, the location of C-2 PNSTs is in most cases posterior to the lateral mass of the atlas and axis and the atlantoaxial joint and is exposed to the posterior without any bone cover. Radical tumor resection is safe, resolution of clinical symptoms is rapid, and recurrence rates are extremely low. In a selected number of cases, bone work for tumor exposure and resection can be entirely avoided.

Anterior reconstruction using titanium plates and locking screws for stabilization of the subaxial and cervicodorsal region tuberculosis is a useful adjunct in preventing kyphotic deformity. A satisfactory segmental stability and fusion is achieved by this technique.

Two patients, a 12-year-old girl and an 8-year-old boy, with congenital craniovertebral anomaly and Klippel-Feil syndrome also had a posterior cranial fossa dermoid. The association of these two discrete pathological lesions in the same individual is extremely rare. As both lesions are related to an embryological disorder, issues regarding the possible stage of dysgenesis are analyzed. The treatment options in such cases are discussed.