Genetic changes in brain tumors and their impact on surgical management

Overview

Brain tumors are abnormal growths in the brain that can be classified into different types based on their genetic mutations. Recent advances in genetic sequencing technologies have allowed for the identification of specific genetic changes in brain tumors, which have significant implications for their management, including surgical management.?

Glioblastoma (GBM), the most common and aggressive type of primary brain tumor in adults is characterized by a number of genetic mutations, including mutations in the tumor suppressor genes TP53 and PTEN, as well as amplification of the epidermal growth factor receptor (EGFR) gene. These genetic changes can affect the tumor growth and response to treatment, as well as its invasive behavior and ability to form blood vessels (angiogenesis).

Genetic Profiling

Glioblastoma?

In terms of surgical management, genetic profiling of glioblastoma can help identify specific molecular targets for therapy, such as EGFR inhibitors or anti-angiogenic agents. In addition, genetic profiling can help guide the extent of surgical resection, as tumors with certain genetic mutations may be more amenable to complete resection than others. For example, studies have suggested that patients with glioblastoma who have mutations in the isocitrate dehydrogenase (IDH) gene may benefit from more extensive surgical resection, the IDH mutation has been identified as a predictor of a better prognosis in gliomas. Also, MGMT methylation status predicts favorable treatment response. Other genetic mutations, such as in the TP53 and ATRX genes, have been associated with a poorer prognosis and resistance to treatment, as these tumors tend to be less invasive and have a better prognosis than those without IDH mutations.

Similarly, other brain tumors, such as meningiomas and ependymomas, have also been found to have specific genetic mutations that can impact their management. For example, mutations in the NF2 gene are commonly found in meningiomas, and can influence the aggressiveness of the tumor and the likelihood of recurrence. Also, TERT promoter mutations can alert the treating clinicians about the aggressive nature of disease and possible recurrence?

In ependymomas, mutations in the C11orf95-RELA fusion gene have been associated with a more aggressive tumor behavior and poorer prognosis and 1q gain has poor prognosis.

Astrocytoma

Astrocytomas (malignancy grade II), anaplastic astrocytomas (malignancy grade III), and glioblastomas are examples of adult diffuse astrocytic tumors (malignancy grade IV). Astrocytoma malignancy grade II tumors have a high occurrence between the ages of 25 and 50, whereas glioblastomas have a peak incidence between the ages of 45 and 70. Around 60% of astrocytomas (malignancy grade II) exhibit allele loss on 17p, including the TP53 gene, and the majority of cases contain a mutant TP53 allele. The lack of wild type p53 is thus the most prevalent aberrant finding in grade II astrocytomas, resulting in a non-functional p53 pathway. A tiny fraction of tumors can have one allele mutated but maintain one wild type allele.

Pilocytic astrocytoma with characteristic BRAF genetic mutation can guide us with targeted therapy. Similarly, the more aggressive midline gliomas in children with H3K27M mutation and mE 3 loss can guide us with future targeted therapy.

Medulloblastoma

Medulloblastoma is more common in kids, although it can develop in adults as well. Childhood and adult medulloblastoma are histologically similar, having highly cellular, malignant invasive tumors of WHO malignancy grade IV. Medulloblastomas arise in the posterior fossa. Iso-chromosome 17q is the most prevalent chromosomal aberration in medulloblastomas, in which much of the short arm of two chromosomes 17 is lost and they are subsequently merged head-to-head, generating a chromosome with two centromeres, little 17p, and two 17q arms. Using cytogenetic approaches, this is seen in 30-50% of instances. CGH and molecular genetic research have corroborated these results.

Genetic testing can be performed on tissue samples obtained during surgery, allowing for the identification of specific mutations and alterations that can guide treatment decisions. In addition, intraoperative molecular diagnosis, such as fluorescence-guided surgery, can help identify tumor boundaries and aid in the removal of as much of the tumor as possible while preserving normal brain tissue.

Advances in molecular imaging techniques, such as magnetic resonance spectroscopy (MRS) and positron emission tomography (PET), can also aid in preoperative planning by providing information on tumor metabolism and identifying regions of increased metabolic activity. Surgical management of brain tumors is often guided by the location and size of the tumor, as well as the extent of resection that can be safely achieved. However, with the increasing understanding of the molecular makeup of brain tumors, surgical management is becoming increasingly personalized.

Conclusion

The purpose of all histology is to offer the doctor with as much helpful information as possible based on an investigation of the tissue obtained, telling the patients of all the specifics of any pathological process present, and providing the foundation for the selection of the most appropriate treatment and a prognosis assessment. Until recently, this method was mostly dependent on morphological analysis. In daily practice, high-throughput assays that can screen numerous genes at once are critical for pathological diagnosis, and Next-generation sequencing (NGS) technology has made this feasible. Genetic changes within brain tumors can have a significant impact on surgical management, with the complete knowledge of gene expression of each type of tumor the extent of surgical resection and can easily be decided to reduce the future recurrence and spread.