Intratumoral Genomic Heterogeneity May Hinder Precision Medicine Strategies in Patients with Serous Ovarian Carcinoma

Abstract

Precision medicine, which includes comprehensive genome sequencing, is a potential therapeutic option for treating high-grade serous carcinoma (HGSC). However, HGSC is a heterogeneous tumor at the architectural, cellular, and molecular levels. Intratumoral molecular heterogeneity currently limits the precision of medical strategies based on the gene mutation status. This study was carried out to analyze the presence of 160 cancer-related genetic alterations in three tissue regions with different pathological features in a patient with HGSC. The patient exhibited histological heterogeneous features with different degrees of large atypical cells and desmoplastic reactions. TP53 mutation, ERBB2 and KRAS amplification, and WT1, CDH1, and KDM6A loss were detected as actionable gene alterations. Interestingly, the ERBB2 and KRAS amplification status gradually changed according to the region examined. The difference was consistent with the differences in pathological features. Our results demonstrate the need for sampling of the appropriate tissue region showing progression of pathological features for molecular analysis to solve issues related to tumor heterogeneity prior to developing precision oncology strategies.

Estimating copy number using next-generation sequencing to determine ERBB2 amplification status

“…Libraries were generated from 80 (DIN ≤ 2.5) or 160 (DIN > 2.5) ng of DNA per sample using the Human Comprehensive Cancer Panel, GeneRead DNAseq Panel PCR kit V2, GeneRead DNA Library I Core Kit, and GeneRead DNA Library I Amp Kit (Qiagen, Hilden, Germany) and the library quality was assessed using the Agilent D1000 ScreenTape (Agilent Technologies). Targeted amplicon exome sequencing was performed using a 160 cancer-related gene panel as previously described [ 18 , 19 ]. The targeted regions of all 160 genes were specifically enriched using oligonucleotide probes.…”

Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer

“…Next-generation sequencing of the EIATs was performed as previously reported [ 12 ]. In brief, DNA integrity was first checked by calculating the DNA unity number using Agilent 2000TapeStation (Agilent Technologies, Santa Clara, CA, USA) prior to targeted amplicon whole-exome sequencing with the Illumina MiSeq sequencing platform (Illumina, San Diego, CA, USA).…”

Dynamic Cancer Cell Heterogeneity: Diagnostic and Therapeutic Implications

“…However, for functional molecular biology, e.g., gene expression, results for samples containing 20 to 30% cancer cells may be misleading in terms of interpretation, and therefore for adequate therapeutic options. Indeed, several studies demonstrate the need to overcome issues related to tumor heterogeneity prior to developing precision oncology strategies by showing that multiple regions of the same tumor can present different morphological and genetic features [ 150 , 151 ]. Moreover, the relatively slow-cycling, low-frequency stem cell phenotype populations may be those most involved in recurrences [ 152 ].…”