A Comparison of DNA Mutation and Copy Number Profiles of Primary Breast Cancers and Paired Brain Metastases for Identifying Clinically Relevant Genetic Alterations in Brain Metastases.

ABSTRACT: Improving the systemic treatment of brain metastases (BM) in primary breast cancer (PBC) is impaired by the lack of genomic characterization of BM. To estimate the concordance of DNA copy-number-alterations (CNAs), mutations, and actionable genetic alterations (AGAs) between paired samples, we performed whole-genome array-comparative-genomic-hybridization, and targeted-next-generation-sequencing on 14 clinical PBC-BM pairs. We found more CNAs, more mutations, and higher tumor mutational burden, and more AGAs in BM than in PBC; 92% of the pairs harbored at least one AGA in the BM not observed in the paired PBC. This concerned various therapeutic classes, including tyrosine-kinase-receptor-inhibitors, phosphatidylinositol 3-kinase/AKT/ mammalian Target of Rapamycin (PI3K/AKT/MTOR)-inhibitors

SUBMITTER: Tyran M 

PROVIDER: S-EPMC6562582 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature