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Cell-free DNA mutations as biomarkers in breast cancer patients receiving tamoxifen

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 ca...

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Detalles Bibliográficos
Autores principales: Jansen, Maurice P.H.M., Martens, John W.M., Helmijr, Jean C.A., Beaufort, Corine M., van Marion, Ronald, Krol, Niels M.G., Monkhorst, Kim, Trapman-Jansen, Anita M.A.C., Meijer-van Gelder, Marion E., Weerts, Marjolein J.A., Ramirez-Ardila, Diana E., Jan Dubbink, Hendrikus, Foekens, John A., Sleijfer, Stefan, Berns, Els M.J.J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190033/
https://www.ncbi.nlm.nih.gov/pubmed/27270325
http://dx.doi.org/10.18632/oncotarget.9727
Descripción
Sumario: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.