Mutational Profile of Metastatic Breast Cancers Analyzed

The authors generated a significant collection of whole-exome sequencing data from the DNA of breast cancer metastases and from each patient’s corresponding unmutated DNA in order to identify mutations and gene copy number alterations specific to the tumors.

Genomic DNA was captured using Agilent in-solution enrichment methodology followed by 75-base paired-end massively parallel sequencing on HiSeq2500, HiSeq4000, or NextSeq500. The bioinformatics analyses identified recurrently mutated genes in metastatic tumors and revealed the genes specifically involved in metastatic disease by comparing their mutational frequency to those of primary breast tumors. The study allowed identification of the affected genes and of mutational signatures that were more prevalent in metastatic as compared with primary tumors and that may be involved in the resistance to therapies.

The identification of mutational and copy number alterations specifically involved in breast cancer metastasis demonstrated that tumors evolve under the pressure of therapy. Characterization of mutations and copy number alterations in metastatic lesions in addition to primary tumors should help to tailor treatment for patients, with the potential for improved clinical outcomes. The authors concluded that their study demonstrated that profiling metastatic cancer can be a major step in defining optimal treatments for patients, as new mutation events and processes may arise during cancer treatment. The study was published on December 27, 2016, in the journal Public Library of Science Medicine.