Mesenchymal-type genetic mutations are likely pre-requisite for glioblastoma multiforme to metastasize outside the central nervous system: an original case series and systematic review of the literature.

in World neurosurgery by Bryce J Laurin, Randall Treffy, Jennifer M Connelly, Michael Straza, Wade M Mueller, Max O Krucoff

TLDR

  • The study found that some GBMs can spread outside the brain to other parts of the body. The study looked at 139 studies and 211 patients with metastatic GBM. The study found that metastases were discovered near previous surgical sites in at least 36.9% of cases. The study also found that the genetic mutations in the metastatic lesions were different from the genetic mutations in the primary GBM lesion. The study suggests that GBMs acquire new mutations to survive outside the brain. The study also highlights the importance of genetic profiling of primary and metastatic lesions in understanding the mechanisms of spread. Future studies should focus on identifying the specific genetic mutations that enable GBMs to spread outside the brain and on developing targeted therapies to treat these mutations.

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and prevalent type of malignant brain tumor, yet they metastasize outside of the central nervous system (CNS) in 0.4% of all cases. Little is known about what enables this subset of GBMs to take root outside the CNS, but genetic mutations likely play a role. We conducted a PRISMA-compliant systematic review of metastatic GBM wherein we reviewed 3579 search results and 1080 abstracts, ultimately analyzing data from 139 studies and 211 unique patients. Additionally, we describe four cases of patients with pathologically confirmed GBM metastases outside the CNS treated at our institution. We found that metastases were discovered near previous surgical sites in at least 36.9% of cases. Other sites of metastasis included bone (47.9%), lung (25.6%), lymph nodes (25.1%), scalp (19.2%), and liver (14.2%). On average, metastases were diagnosed 12.1 months after the most recent resection, and the mean survival from discovery was 5.7 months. In our patients, primary GBM lesions revealed mutations in NF1, TERT, TP53, CDK4, and RB1/PTEN genes. Unique to the metastatic lesions were amplifications in genes such as p53 and PDGFRA/KIT, as well as increased vimentin and Ki-67 expression. In sum, there is strong evidence that GBMs acquire novel mutations to survive outside the CNS. In some cases, tumor cells likely mutate after seeding scalp tissue during surgery, and in others, they mutate and spread without surgery. Future studies and genetic profiling of primary and metastatic lesions may help uncover the mechanisms of spread.

Overview

  • The study aims to investigate the genetic mutations that enable GBMs to metastasize outside the CNS. The study conducted a systematic review of 139 studies and 211 unique patients with metastatic GBM. Additionally, the study describes four cases of patients with pathologically confirmed GBM metastases outside the CNS treated at the authors' institution. The primary objective of the study is to identify the genetic mutations that enable GBMs to metastasize outside the CNS and to understand the mechanisms of spread.

Comparative Analysis & Findings

  • The study found that metastases were discovered near previous surgical sites in at least 36.9% of cases. Other sites of metastasis included bone (47.9%), lung (25.6%), lymph nodes (25.1%), scalp (19.2%), and liver (14.2%). On average, metastases were diagnosed 12.1 months after the most recent resection, and the mean survival from discovery was 5.7 months. In the four cases of patients with pathologically confirmed GBM metastases outside the CNS treated at the authors' institution, primary GBM lesions revealed mutations in NF1, TERT, TP53, CDK4, and RB1/PTEN genes. Unique to the metastatic lesions were amplifications in genes such as p53 and PDGFRA/KIT, as well as increased vimentin and Ki-67 expression. The study provides strong evidence that GBMs acquire novel mutations to survive outside the CNS.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice. The study identifies the genetic mutations that enable GBMs to metastasize outside the CNS, which can inform the development of new treatments and therapies. The study also highlights the importance of genetic profiling of primary and metastatic lesions in understanding the mechanisms of spread. Future studies should focus on identifying the specific genetic mutations that enable GBMs to metastasize outside the CNS and on developing targeted therapies to treat these mutations. Additionally, future studies should investigate the role of scalp tissue in the development of GBM metastases and the potential for scalp tissue to be used as a biomarker for GBM metastasis.
Read Full Article