Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling
| Autor: | Jan Frisell, Johan Lindberg, Johan Hartman, Lena Wedlund, Jonas Bergh, Ikram Ullah, Ran Ma, Amjad Alkodsi, Govindasamy-Muralidharan Karthik, Mattias Rantalainen, Gustav Stålhammar, John Lövrot |
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| Přispěvatelé: | Research Programs Unit, Genome-Scale Biology (GSB) Research Program, Sampsa Hautaniemi / Principal Investigator, University of Helsinki |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
HISTOLOGIC GRADE
0301 basic medicine Cancer Research Pathology medicine.medical_specialty Microarray Molecular subtypes 3122 Cancers Breast Neoplasms Computational biology Biology lcsh:RC254-282 SUBTYPES Transcriptome Intra-tumor transcriptomic heterogeneity 03 medical and health sciences Genetic Heterogeneity 0302 clinical medicine Breast cancer Surgical oncology Genetics medicine Molecular diagnostics Biomarkers Tumor Humans ASSAY Gene Regulatory Networks TREATMENT DECISIONS Exome sequencing GENE-EXPRESSION DATA Sequence Analysis RNA Gene Expression Profiling SIGNATURE QUANTIFICATION lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Subtyping 3. Good health Gene Expression Regulation Neoplastic ESTROGEN-RECEPTOR 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cohort Female Research Article |
| Zdroj: | BMC Cancer BMC Cancer, Vol 17, Iss 1, Pp 1-11 (2017) |
| ISSN: | 1471-2407 |
| Popis: | Background Transcriptomic 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. Methods In 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. Results Molecular 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. Conclusions Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients. Electronic supplementary material The online version of this article (10.1186/s12885-017-3815-2) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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