GEN-1 ORIGINALLY DEVELOPED TUMOR SAMPLER TO REVEAL INTRATUMORAL HETEROGENEITY IN BRAIN TUMORS

Abstract

Abstract Intratumor heterogeneity has been analyzed in brain tumors, and it has revealed that clonal evolution results in the formation of genetically diverse cell populations, which is a major factor in treatment resistance and recurrence. However, intratumoral heterogeneity has not been analyzed in routine clinical practice and remains at the research level. Here, we developed a novel tumor sampler to establish the analysis of intratumoral heterogeneity as a routine clinical procedure and to clarify its clinical significance in brain tumors. Our novel tumor sampler consists of a hollow cylinder with a lid, which enabled us to obtain a cylindrical tumor sample cross-sectionally by inserting from the tumor surface to the depth, like the geological borehole test. The obtained cylindrical sample was divided vertically into two, one for pathological analysis and one for genetic analysis, which allowed us to compare genetic findings and pathological findings in arbitrary site of the sample. The sampling procedure was simple and completed in a short time, allowing comparison of heterogeneity among a large number of cases. We collected samples from four cases of Glioblastoma and three cases of brain metastasis using the sampler, and analyzed intratumoral heterogeneity by identifying somatic mutations at multiple sites by whole exome sequencing. We evaluated genetic and morphological heterogeneity among each site, generated a phylogenetic tree of clonal evolution within the tumor, and confirmed that these data could be compared among the cases. Using our novel tumor sampler could establish the analysis of intratumoral heterogeneity as a routine clinical procedure, and it expected to have a significant impact on treatment strategies for brain tumors.