Journal
ONCOTARGET
Volume 7, Issue 28, Pages 43412-43418Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9727
Keywords
breast cancer; tamoxifen therapy; targeted next generation sequencing; cell-free DNA; disease progression
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Funding
- NWO-Cancer Genomics Netherlands
- Nijbakker-Morra Foundation, Leiden, The Netherlands
- Merck KGaA, Darmstadt, Germany
- MRace, Rotterdam, The Netherlands
- Philips Research
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The aim was to identify mutations in serum cell-free DNA (cfDNA) associated with disease progression on tamoxifen treatment in metastatic breast cancer (MBC). Sera available at start of therapy, during therapy and at disease progression were selected from 10 estrogen receptor (ER)-positive breast cancer patients. DNA from primary tumor and normal tissue and cfDNA from minute amounts of sera were analyzed by targeted next generation sequencing (NGS) of 45 genes (1,242 exons). At disease progression, stop-gain single nucleotide variants (SNVs) for CREBBP (1 patient) and SMAD4 (1 patient) and non-synonymous SNVs for AKAP9 (1 patient), PIK3CA (2 patients) and TP53 (2 patients) were found. Mutations in CREBBP and SMAD4 have only been occasionally reported in breast cancer. All mutations, except for AKAP9, were also present in the primary tumor but not detected in all blood specimens preceding progression. More sensitive detection by deeper re-sequencing and digital PCR confirmed the occurrence of circulating tumor DNA (ctDNA) and these biomarkers in blood specimens.
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