Molecular Diagnostics in Central Nervous System Tumors

Abstract

Central nervous system (CNS) neoplasms can be diagnostically challenging, due to remarkably wide ranges in histologic appearance, biologic behavior, and therapeutic approach. Nevertheless, accurate diagnosis is the critical first step in providing optimal patient care. As with other oncology-based specialties, there is a rapidly expanding interest and enthusiasm for identifying and utilizing new biomarkers to enhance the day-to-day practice of surgical neuropathology. In this regard, the field is primed by recent advances in basic research, elucidating the molecular mechanisms of tumorigenesis and progression in the most common adult and pediatric brain tumors. Thus far, few have made the transition into routine clinical practice, the most notable example being 1p and 19q testing in oligodendroglial tumors. However, the field is rapidly evolving and many other biomarkers are likely to emerge as useful ancillary diagnostic, prognostic, or therapeutic aids. The goal of this article is to highlight the most common genetic alterations currently implicated in CNS tumors, focusing most on those that are either already in common use in ancillary molecular diagnostics testing or are likely to become so in the near future.

Screening of Glioma Patients for 1p/19q Region with Fluorescent Probes

“…We have found that tumors developing in the frontal lobe were of a much higher incidence of 1p/19q loss. Loss of 1p/19q is considered a strong prognostic factor reported to occur in 50 -90% of oligodendroglial tumors and around 27-50% of oligoastrocytomas and is comparatively lower (8 to 25%) in Ass [15][16][17][18][19]. Our results in OG tumors showed combined 1p/19q loss in 60% which included 38% of grade II and 61.9% of grade III OGs.…”

Meningiomas exhibit loss of heterozygosity of the APC gene

“…Up to 60% of meningiomas carry inactivating mutations in the remaining NF2 allele. Loss of expression of NF2 protein product merlin is consistent finding in all NF2 associated meningiomas and in about half of sporadic benign cases [11]. Relevant genetic alterations of atypical and anaplastic meningiomas are still unknown.…”

Genetic and protein changes of E-cadherin in meningiomas

“…Up to 60% of meningiomas carry inactivating mutations in the remaining NF2 allele. Loss of expression of NF2 protein product merlin is consistent finding in all NF2 associated meningiomas and in about half of sporadic benign cases (Fuller and Perry 2005). Relevant genetic alterations of atypical and anaplastic meningiomas are still unknown.…”