Molecular diagnosis of brain tumors

K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released June 17, 1997; last updated October 12, 2020; expires October 12, 2023


Recognition of cancer as a genetic disorder has opened the possibility of classifying tumors according to genetic alterations that underlie their pathogenesis and regulate their malignant behavior. Genetic analysis is now assuming importance in the diagnosis, classification, and prognosis of brain tumors. This article describes the application of molecular diagnostic techniques as aids to the laboratory diagnosis of brain tumors, as well as to investigation of molecular genetics of tumors. Refinements in molecular imaging technologies such as PET provide the most sensitive and specific techniques for quantitative assessment of a brain tumor's pathophysiology, gene expression, and biochemistry.

Key points


• Traditional diagnosis of malignancy in brain tumors was based on imaging, histological examination, and cytogenetics.


• Next generation sequencing of gene mutations associated with malignancy is an important contribution to diagnosis.


• Refinements in molecular diagnostics have improved diagnosis, understanding of molecular biology of malignancy, and determination of prognosis.


• Detection of circulating tumor DNA in CSF can be an alternative diagnostic method as liquid biopsy of gliomas.


• Molecular diagnosis is useful for personalizing the treatment of primary malignant brain tumors, particularly glioblastoma.

Historical note and terminology

For molecular diagnostic purposes, brain tumors may be divided into benign and malignant (primary or secondary) categories, although this distinction is not always clear-cut. Benign tumors include meningiomas (these have a malignant form as well) and acoustic neuromas (that may be part of inherited tumor syndromes). The major concern is diagnosis of malignancy; this is performed routinely by examination of the tumor sample and is being extended to diagnosis in vivo. The most common primary malignant tumor of the brain in adults is glioblastoma. Other common forms are malignant varieties of ependymoma and oligodendroglioma. The most common primary malignant brain tumor in children is medulloblastoma. Tumors from any part of the body can metastasize to the brain; these are nearly as common as primary malignant tumors of the brain. Meningeal metastases from cancer have become an increasing problem as the treatment of systemic disease improves. Meningeal malignancy results from metastases of intracranial or extracranial tumors to the coverings of the brain (pia and arachnoid).

In the past, most of the genetic studies of tumors involved cytogenetic analysis. These studies can detect gross chromosomal abnormalities, numerical or structural. Numerical abnormalities involve the loss or gain of parts of chromosomes or whole chromosomes or the gain of an entire complement of chromosomes. Structural alterations include deletions, duplications, inversions, and translocations. Karyotype analysis requires that the cells are actively dividing and may not be easily applicable to solid tumors with a low mitotic index. Culturing cells can introduce cytogenetic aberrations. Limitations of cytogenetic techniques are that they can detect changes in the genome only if the size of the region involved is greater than 3000 to 5000 kb. Loss of genetic material detected by these techniques may affect many genes simultaneously. The findings may give a clue of where to look for more detailed changes by molecular methods. Important contributions to the diagnosis of CNS malignancy include detection and sequencing of circulating tumor cells in CSF.

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