Biomedical subjects

Wai-In Chan

Publications and source records attributed to Wai-In Chan.

4 recordsLinked to original sources

PubMed2005

CIC, a gene involved in cerebellar development and ErbB signaling, is significantly expressed in medulloblastomas.

In children, the majority of brain tumors arise in the cerebellum. Medulloblastomas, the most common of these, are believed to originate from the granule cell lineage. We have recently identified a mammalian gene, capicua (Cic), the ortholog of a Drosophila gene implicated in c-erbB (Egfr) signaling, which is predominantly expressed during mouse granule cell development. Its expression in medulloblastoma is therefore of particular interest. In the present study the expression of human CIC in medulloblastoma was analyzed. In silico SAGE analysis demonstrated that medulloblastomas exhibited the highest level of CIC expression and expression was most common in tumors of the CNS in general. RT-PCR and in situ hybridization verified the expression of CIC in tumor cells, although the level of expression varied between different medulloblastoma subtypes. The expression of CIC did not correlate with other markers, such as neurofilament, GFAP and Mib-1. In postnatally developing cerebellum, in silico analysis and in situ hybridization both indicated a strong correlation between Cic expression and the maturation profile of cerebellar granule cell precursors. Expression of CIC is therefore a feature shared between immature granule cells and the tumors derived from them. Cic has been implicated as a mediator of ErbB signaling and this pathway has been associated with a poor prognosis for medulloblastomas. Therefore, further analysis of the role of Cic is likely to provide valuable insight into the biology of these tumors. Additionally, study of genes such as CIC should provide objective criteria by which, in combination with other markers and clinical data, to categorize these tumors into subgroups that might allow better allocation into specific treatment regimes.

Biomarkers↗

PubMed2004

Novel strategy to study gene expression and function in developing cerebellar granule cells.

The advent of techniques for global analyses of cell biology, such as genomics and proteomics, opens the way to rapid progress in understanding the molecular control of developing tissues. However, such studies in the CNS are hindered by the complexity of this tissue. In particular, few approaches allow cells to be isolated that are enriched for specific stages of their maturation. We describe a new strategy to study gene expression and function in cerebellar granule cells. In these experiments, we have used square pulse electroporation to introduce fluorescent dye or DNA constructs into immature granule cell precursors in situ. This method only labels granule cell precursors in the superficial part of the external granule layer. Combining this labelling with fluorescent activated cell sorting (FACS) allows the transfected cells to be isolated at any time during their subsequent development, thus providing a means of analysing granule cells as they undergo maturation. This transfection method can be used to study events in the normal maturation of granule cells or the effects of introduced transgenes. Such studies can be carried out on cells purified from primary cultures or cells in situ using cerebellar slice cultures. Our strategy provides a new route to detailed analysis of the role of genes in controlling many aspects of granule cell biology. These approaches will allow recent global analyses to be more readily applied to subpopulations of cells in complex tissues.

Animals↗

PubMed2002

CIC, a member of a novel subfamily of the HMG-box superfamily, is transiently expressed in developing granule neurons.

We describe here the identification and characterization of a new gene, Cic, in both human and mouse genomes. These are orthologs of the Drosophila gene capicua, and represent a new subfamily of the HMG-box superfamily. Expression of the Cic gene is predominantly restricted to immature granule cells in the cerebellum, hippocampus and olfactory bulb in the CNS. This gene is therefore implicated in CNS development, in particular in granule cell development.

Amino Acid Sequence↗

PubMed2002

Differential expression of SOX4 and SOX11 in medulloblastoma.

Primitive neuroectodermal tumors (PNETs) are composed of immature neuronal precursor cells and sometimes more mature neuronal cell types. Medulloblastomas, occuring in the cerebellum, represent the most common PNET and are broadly classified into two subgroups: classical and desmoplastic. Desmoplastic medulloblastomas exhibit a slightly better prognosis than classical medulloblastomas. However, there are currently no good molecular markers available to distinguish clinical outcome and similar treatment is used for most patients with associated complications. It has been shown that neoplastic cells in these tumors recapitulate stages in maturation of normal human neuroblasts; therefore, embryological studies of the earliest events in the development of the cerebellum may provide useful information about the molecular behavior of the tumor. Transcription factors such as Sox proteins involved in neural development may also play a role in the etiology of brain tumors. Sox4 in particular has been implicated in the biology of several other types of cancer. We have studied the expression of Sox4, and the closely related Sox11 gene, in medulloblastomas. Sox4 and Sox11 were strongly expressed in most classical medulloblastomas but only weakly in desmoplastic medulloblastomas. The expression profile of these two genes in developing cerebellum was also analyzed. Our results suggest that strong Sox4 and Sox11 expression in classical medulloblastomas reflects their maturation-dependent expression during normal cerebellum development, and that they may therefore provide markers to divide tumors into clinically relevant subgroups.

Biomarkers, Tumor↗