Mario Suzuki

A functional screening of the kinome identifies the Polo-like kinase 4 as a potential therapeutic target for malignant rhabdoid tumors, and possibly, other embryonal tumors of the brain

Malignant rhabdoid tumors (MRTs) are deadly embryonal tumors of the infancy. With poor survival and modest response to available therapies, more effective and less toxic treatments are needed. We hypothesized that a systematic screening of the kinome will reveal kinases that drive rhabdoid tumors and can be targeted by specific inhibitors.

Overexpression of TEAD4 in atypical teratoid/rhabdoid tumor: New insight to the pathophysiology of an aggressive brain tumor

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal brain tumor that occurs mainly in early childhood. Although most of the tumors are characterized by inactivating mutations of the tumor suppressor gene, SMARCB1, the biological basis of its tumorigenesis and aggressiveness is still unknown.

Prosthetic material degeneration over time as a possible factor in delayed recurrence of hemifacial spasm after successful microvascular decompression

Background: The effectiveness of microvascular decompression in treating hemifacial spasm is widely accepted. However, some experience recurrence of hemifacial spasm after successful decompression surgery. Especially, delayed recurrence more than 5 years after surgery is rare and the cause of this phenomenon is unknown. Case Description: A female underwent microvascular decompression to treat her hemifacial spasm 6 years ago. Six years later, her hemifacial spasm recurred and she underwent a second surgery. The second surgery revealed that the sponge had become fragile, losing the ability to absorb the impact of pulsatile compression of the offending artery on the root exit zone of her facial nerve. Conclusion: We report a case in which degeneration of material, a sponge (polyurethane), used in decompression surgery caused delayed recurrence of hemifacial spasm. The selection of appropriate prosthetic materials is essential in such functional surgeries.

A Comprehensive Method for Detecting Fusion Genes in Paediatric Brain Tumours

Background: Fusion genes driving tumourigenesis have drawn the attention of researchers and oncologists. Despite the importance of such molecular alterations, there are no comprehensive reproducible methods for detecting fusion genes. Materials and Methods: Nineteen paediatric brain tumours of five types, namely pilocytic astrocytoma, oligodendroglioma, anaplastic astrocytoma, glioblastoma and, ganglioglioma, were examined to detect fusion genes using a pyrosequencing-based method following RNA isolation, cDNA synthesis and real-time polymerase chain reaction. Results: Our method successfully detected KIAA1549–v-raf murine sarcoma viral oncogene homolog B1 (BRAF) fusion in 14 out of 19 patients suffering from five types of paediatric brain tumours providing information on fusion breakpoints within 2 h. Conclusion: A comprehensive method for detecting fusion genes in paediatric brain tumours was evaluated. This method identified KIAA1549–BRAF fusion variants quickly. Our results may help researchers interested in the role of fusion genes in tumourigenesis.

Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

BackgroundAtypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors of the central nervous system. They are largely characterized by inactivating mutations of the SMARCB1 tumor suppressor gene. AT/RT patients have a very poor prognosis and no standard therapeutic protocol has been defined yet. Recently, multimodal therapy with multiple drug combinations has slightly improved the overall survival, however drug toxicity remains high. In this scenario, a better understanding of the pathophysiology of the disease is needed.MethodsWe evaluated the gene expression profile of AT/RT samples to find new genetic factors contributing to the pathophysiology of the disease. We found target genes significantly differentially expressed between AT/RT and medulloblastoma (MB), the most common embryonal brain tumor. The mRNA expression was validated by quantitative real-time PCR and, at the protein level, expression was validated by immunohistochemistry in an independent set of tumors.ResultsThe Neural cell adhesion molecule 1 (NCAM1) gene was found to be consistently downregulated in AT/RT samples when compared to MB and normal brain tissue. Immunohistochemistry showed that the expression of NCAM1 in AT/RT was significantly lower than that of MB.ConclusionNCAM1 is an important molecule involved in neuron-to-neuron and neuron-to-muscle adhesion during development. Downregulation of NCAM1 has been implicated in several human cancers suggesting that it might have a tumor repressor role. In this study we found a significantly reduced expression of NCAM1 in AT/RT when compared to MB and we suggest that this feature can be used as a diagnostic marker, along with demonstration of SMARCB1 (INI1) or SMARCA4 (BRG1) inactivation. The roles of NCAM1 in the pathophysiology of AT/RT are still to be determined.