Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling

Abstract

BackgroundTranscriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics.MethodsIn this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications.ResultsMolecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications.ConclusionsOur results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3815-2) contains supplementary material, which is available to authorized users.

Re-testing of predictive biomarkers on surgical breast cancer specimens is clinically relevant

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Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas

“…post transcriptional modification, translational and protein degradation regulation [29, 30]. It has been reported that intratumoral heterogeneity has limited impact on gene expression profiling and can be easily detected using IHC [31, 32].…”

SH003 Causes ER Stress-mediated Apoptosis of Breast Cancer CellsviaIntracellular ROS Production

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