65. Insights into the genetic heterogeneity of glioblastoma: gene amplification in ecDNA and HSR

Aly Abdelkareem

Inés Martín Barrio

Inés Martín Barrio is a dedicated graduate student enrolled in the Master of Science in Diagnostic Genetics and Genomics program at the University of Texas MD Anderson Cancer Center School of Health Professions. She specializes in the cytogenetics track and is set to graduate August 2023.

Inés is originally from Madrid, Spain, where she earned her Bachelor of Science in Genetics from the esteemed San Pablo CEU University. Throughout her academic journey, she has shown remarkable interest in the field of cytogenetics and genetics in general.

During her final year as a graduate student, Inés has been actively involved in research at the laboratory of Dr. Kadir Akdermir, Ph.D. Her work has focused on utilizing cytogenetic techniques, such as FISH (Fluorescent in situ hybridization) and SKY (Spectral Karyotyping), to investigate mutations observed in patients’ derived glioblastoma cell lines. Her findings have been integral in validating genomic results generated by her fellow colleagues in the lab using molecular techniques, which has enabled the team to present their research at multiple conferences and meetings.


Inés Martín Barrioa, Bo Zhaob, Lingqun Yeb, Xiaojun Liuc, Peter Huc Awdhesh Kaliac, Yonathan Lissanud, Manjunath Nimmakayaluc, Kadir Akdemire

aUTH SHP MD Anderson Cancer Center, Houston, TX, United States; bMD Anderson Cancer Center, Houston, TX, United States; cSHP MD Anderson Cancer Center, Houston, TX, United States; dThoracic & Cardio Surgery-Rsch MD Anderson Cancer Center, Houston, TX, United States; eNeurosurgery – Research MD Anderson Cancer Center, Houston, TX, United States

Glioblastoma is a highly aggressive brain tumor characterized by genetic heterogeneity and a poor prognosis. Novel mechanisms of gene amplification occur most frequently in glioblastoma, involving extrachromosomal DNA (ecDNA) and homogeneously staining regions (HSR), compared to other human tumor types. ecDNA and HSR are circular DNA fragments and chromosomal regions that contain multiple copies of a particular oncogene, respectively. These genetic abnormal structures are thought to facilitate rapid and extensive gene amplification, leading to the upregulation of oncogenes that promote tumor growth and survival.

The objective of our study is to understand the role of extrachromosomal DNA (ecDNA) and homogeneously staining regions (HSR) in gene amplification in patient-derived glioblastoma cell lines. We analyzed genomic data from a cohort of glioblastoma patients compared to molecular cytogenetics observations and characterized the distribution of gene amplification between ecDNA, and HSR.

Our preliminary findings are in line with the genomic analysis, which includes the detection of a significant EGFR gene amplification in ecDNA structures. Furthermore, our findings indicate that the amplifications of PAX6/WT1 were predominantly in the form of linear HSR.

Overall, our study provides important insights into the mechanisms of gene amplification in glioblastoma and its impact on clinical outcomes. My findings suggest that targeting ecDNA and HSR regions may be a promising strategy for improving treatment outcomes in glioblastoma patients with gene amplification. Further research is needed to develop effective therapies that target these regions and improve overall survival rates in glioblastoma.

Keywords: cytogenomic techniques, ecDNA, HSR, gene amplification.