A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Clinical Epigenetics
Begoña PinedaPilar Eroles

Abstract

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) varies between 30 and 40% approximately. To provide further insight into the prediction of pCR, we evaluated the role of an epigenetic methylation-based signature. Epigenetic assessment of DNA extracted from biopsy archived samples previous to NAC from TNBC patients was performed. Patients included were categorized according to previous response to NAC in responder (pCR or residual cancer burden, RCB = 0) or non-responder (non-pCR or RCB > 0) patients. A methyloma study was performed in a discovery cohort by the Infinium HumanMethylation450 BeadChip (450K array) from Illumina. The epigenetic silencing of those methylated genes in the discovery cohort were validated by bisulfite pyrosequencing (PyroMark Q96 System version 2.0.6, Qiagen) and qRT-PCR in an independent cohort of TN patients and in TN cell lines. Twenty-four and 30 patients were included in the discovery and validation cohorts, respectively. In the discovery cohort, nine genes were differentially methylated: six presented higher methylation in non-responder patients (LOC641519, LEF1, HOXA5, EVC2, TLX3, CDKL2) and three greater methylation in responder pa...Continue Reading

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Citations

Dec 4, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Erick PereraJaume Pérez-Sánchez
Feb 6, 2020·International Journal of Molecular Sciences·Saioa MendazaDavid Guerrero-Setas
Jul 14, 2020·The Journal of Clinical Investigation·Matt R PaulLewis A Chodosh
Sep 12, 2019·Current Cancer Drug Targets·Aamir Ahmad
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Mar 25, 2021·Seminars in Cancer Biology·Javier OliverIsabel Barragan
Aug 14, 2021·RNA Biology·Erika Pereira ZambaldeJaqueline Carvalhode Oliveira
Aug 11, 2020·Breast Care·Mercedes Herrera JuarezEva Ciruelos Gil

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Methods Mentioned

BETA
GTPases
biopsies
GTPase
biopsy
electrophoresis
Assay

Software Mentioned

GraphPad Prism
Prosigna
R
Pathway Commons
Oncotype
MammaPrint
GenomeStudio Illumina
Endopredict
Blue

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