Biomarkers in Neoplastic Neuropathology

Book Preface

Current Biomarkers in Neoplastic Neuropathology

Enormous advances have been achieved in recent years in our understanding of the molecular basis of cancers, particularly those affecting the nervous system. Many of these advances have been propelled by sequencing of the human genome of all major cancers, greater availability of high-throughput analytic techniques, and large, publically available databases such as that created by The Cancer Genome Atlas (TCGA). The TCGA was pioneered in the study of glioblastoma and aims to provide a comprehensive, multidimensional picture of all major human cancers. More recently, the whole spectrum of diffuse gliomas (astrocytomas and oligodendrogliomas grades II–III) were also studied under the umbrella of “lower grade glioma.” Many of these studies have generated increased complexity and vast amounts of data which, although comprehensive, make it challenging to identify key markers for molecular diagnosis and therapeutic targeting. A major challenge resides in incorporating this molecular data in the context of tissue-based techniques that have resided in the realm of neuropathology, including routine histologic examination and immunohistochemistry. In the current text, we describe the status of biomarkers applicable to the pathology of neoplastic disorders of the brain. First, an overview on the current status of biomarker analysis in brain tumors will be provided, and a discussion on how major scientifi c discoveries are reshaping the current practice of neoplastic neuropathology. Descriptions of the current techniques available for the clinical and experimental evaluation of biomarkers in brain neoplasms are presented, including the classic techniques of immunohistochemistry and in situ hybridization which have provided enormous assistance in diagnosis and prognostication of brain tumors for over a decade now. High-throughput molecular techniques, array-based methods, methylation profi ling, next-generation sequencing, and practical gene panels are fi nding increasing applications in neuropathology practice as robust biomarker tests. As no single technique provides a complete picture of neoplasms in the particular patient, incorporation of multiple biomarkers in the development of molecular subgroups with biologic and therapeutic relevance are discussed, an approach increasingly applied to the study of brain cancer.

As important as these techniques are, optimal preservation of tissue balancing clinical and research needs is an equally important topic that is covered on a section on biobanking. Using tissue obtained in clinical settings also raises important ethical considerations, including tissue ownership and incorporation of patients and their families in decision making. These issues and institutional guidelines are covered. Finally, the major categories of neoplastic disorders involving the nervous system are discussed, with emphasis on diagnostic, prognostic, and predictive biomarkers that are in current use in the pathologic evaluation of brain tumors. Biomarkers resulting from major scientifi c breakthroughs and that have withstood the test of time in neuropathology practice will represent the primary focus, including IDH1 mutations (diffuse gliomas), 1p19 co-deletions (oligodendroglial tumors), MGMT promoter methylation (glioblastoma), BRAF alterations (pediatric gliomas), and molecular subgrouping (medulloblastoma).