publication date: Jan. 31, 2020

Clinical Roundup

Stem cells, CRISPR and gene sequencing technology are basis of brain cancer model

University of California San Diego School of Medicine researchers used genetically engineered human pluripotent stem cells to create a cancer model to study in vivo how glioblastoma develops and changes over time.

“We have developed stem cell models that are CRISPR-engineered to have tumor-associated driver mutations in glioblastoma, which harbor essentially all features of patient-derived tumors, including extrachromosomal DNA amplification,” co-senior author Frank B. Funari, professor in the Department of Pathology at UC San Diego School of Medicine and head of the Laboratory of Tumor Biology in the San Diego branch of the Ludwig Institute for Cancer Research, said in a statement.

“These models, or avatars as we call them, enable us to study human tumor development over long periods in vivo, which has not been feasible with patient-derived tissue samples which already harbor other genetic changes.”

The results of the study were published Jan. 28 in Nature Communications.

Researchers used CRISPR editing to make precise mutations in an otherwise “normal” genome to create the genetic conditions that enable tumor development. The resulting avatars are unique in that they behave like a grade 4 glioma in their level of pathology, transcriptome signatures, and engineered genetic alterations and evolution of genetic mutations, such as the emergence of extrachromosomal DNA and chromosomal rearrangements.

“The addition of single-cell RNA sequencing and computational tools enabled efficient analysis of big data to truly evaluate the surprising intra-tumor heterogeneity present in our avatars which replicates what is seen in patients samples,” co-senior author Gene W. Yeo, professor in the Department of Cellular and Molecular Medicine and the Institute for … Continue reading Stem cells, CRISPR and gene sequencing technology are basis of brain cancer model

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