Evaluating Tumor Evolution via Genomic Profiling of Individual Tumor Spheroids in a Malignant Ascites

Scientific Reports
Sungsik KimYong-Sang Song

Abstract

Epithelial ovarian cancer (EOC) is a silent but mostly lethal gynecologic malignancy. Most patients present with malignant ascites and peritoneal seeding at diagnosis. In the present study, we used a laser-aided isolation technique to investigate the clonal relationship between the primary tumor and tumor spheroids found in the malignant ascites of an EOC patient. Somatic alteration profiles of ovarian cancer-related genes were determined for eight spatially separated samples from primary ovarian tumor tissues and ten tumor spheroids from the malignant ascites using next-generation sequencing. We observed high levels of intra-tumor heterogeneity (ITH) in copy number alterations (CNAs) and single-nucleotide variants (SNVs) in the primary tumor and the tumor spheroids. As a result, we discovered that tumor cells in the primary tissues and the ascites were genetically different lineages. We categorized the CNAs and SNVs into clonal and subclonal alterations according to their distribution among the samples. Also, we identified focal amplifications and deletions in the analyzed samples. For SNVs, a total of 171 somatic mutations were observed, among which 66 were clonal mutations present in both the primary tumor and the ascites, a...Continue Reading

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Citations

Feb 6, 2020·Diagnostic Cytopathology·Ben Davidson
Sep 23, 2020·Biochemical and Biophysical Research Communications·Dong-Wook MinTae-You Kim

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Methods Mentioned

BETA
PCR
MDA
genotyping

Software Mentioned

R
Varscan
MuTect
GATK UnifedGenotyper
Indel
Omni
GATK
Varscan2
GATK VariantRecalibrator
Python

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