Research interests:

Our lab is using microarray technology to determine the downstream consequences of genetic alterations associated with human glial neoplasms; our ultimate goal is to use this information to develop molecular markers for improved clinical management of patients with malignant glioma. In particular, we are analyzing glial tumor samples for gene expression differences within each of: distinct pathological subgroups, distinct molecular genetic subgroups, and groups of patients who have responded to treatment in a unique or distinct fashion.

In modern clinical neuro-oncology, no variable affects prognostic estimation and therapeutic decisions more than tumor classification. In our first microarray study, we investigated whether gene expression profiling could be used to define subgroups of glial tumors in a manner more explicit and consistent than classical pathology. Supervised learning approaches were used to build a two-class model to separate a subset of 14 glioblastomas and 7 anaplastic oligodendrogliomas with classic “textbook” histology. This two-class model was then used to predict a classification for the remaining 29 samples with non-classic “textbook” histology. Classification based on expression profiling provided stronger outcome prediction than did classification based on standard pathology. Moreover, our microarray data identified more than 500 genetic markers that can distinguish between glioblastoma and anaplastic oligodendroglioma subclasses. We are now pursuing the more translational-specific aim of developing immunohistochemical markers for these class distinctions. In one recent study, we demonstrated that one marker, YKL-40, was capable of distinguishing anaplastic oligodendrogliomas from glioblastomas. YKL-40 staining appeared to provide a better class distinction of glioblastoma versus anaplastic oligodendroglioma than GFAP, the current standard immunohistochemical marker used clinically to distinguish diagnostically challenging gliomas. Moreover, a combination of YKL-40 and GFAP immunohistochemistry afforded even greater diagnostic accuracy. We continue to use our initial microarray data to develop additional immunohistochemical markers of this class distinction.

Additional ongoing projects in the lab include: microarray analysis of EGFR amplified and p53-mutated glioblastomas, the most common genetic alterations within these tumors; microarray analysis of a clinically aggressive subset of anaplastic oligodendrogliomas; microarray analysis of chemoresponse in oligodendrogliomas; and the development of immunohistochemical markers for each of these tumor subsets.

Bibliography of Catherine L. Nutt via Pubmed (will open in new window)