Genomic characterization of metastatic breast cancers.

Metastasis is the main cause of death for patients with breast cancer. Many studies have characterized the genomic landscape of breast cancer during its early stages. However, there is evidence that genomic alterations are acquired during the evolution of cancers from their early to late stages, and that the genomic landscape of early cancers is not representative of that of lethal cancers1-7. Here we investigated the landscape of somatic alterations in 617 metastatic breast cancers. Nine driver genes (TP53, ESR1, GATA3, KMT2C, NCOR1, AKT1, NF1, RIC8A and RB1) were more frequently mutated in metastatic breast cancers that expressed hormone receptors (oestrogen and/or progesterone receptors; HR+) but did not have high levels of HER2 (HER2-; n = 381), when compared to early breast cancers from The Cancer Genome Atlas. In addition, 18 amplicons were more frequently observed in HR+/HER2- metastatic breast cancers. These cancers showed an increase in mutational signatures S2, S3, S10, S13 and S17. Among the gene alterations that were enriched in HR+/HER2- metastatic breast cancers, mutations in TP53, RB1 and NF1, together with S10, S13 and S17, were associated with poor outcome. Metastatic triple-negative breast cancers showed an increase in the frequency of somatic biallelic loss-of-function mutations in genes related to homologous recombination DNA repair, compared to early triple-negative breast cancers (7% versus 2%). Finally, metastatic breast cancers showed an increase in mutational burden and clonal diversity compared to early breast cancers. Thus, the genomic landscape of metastatic breast cancer is enriched in clinically relevant genomic alterations and is more complex than that of early breast cancer. The identification of genomic alterations associated with poor outcome will allow earlier and better selection of patients who require the use of treatments that are still in clinical trials. The genetic complexity observed in advanced breast cancer suggests that such treatments should be introduced as early as possible in the disease course.

Author Correction: Genomic characterization of metastatic breast cancers.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Full Sequencing and Genomic Analysis of Three emm75 Group A Streptococcus Strains Recovered in the Course of an Epidemiological Shift in French Brittany.

While the incidence and invasiveness of type emm75 group A Streptococcus (GAS) infections increased in French Brittany during 2013, we sequenced and analyzed the genomes of three independent strains isolated in 2009, 2012, and 2014, respectively. In this short-term evolution, genomic analysis evidenced mainly the integration of new phages encoding virulence factors.

Genome Sequence of the Uncommon Streptococcus pyogenes M/emm66 Strain STAB13021, Isolated from Clonal Clustered Cases in French Brittany.

Here, we announce the complete annotated genome sequence of the invasive Streptococcus pyogenes strain M/emm66, isolated in 2013 from a subcutaneous abscess in new clustered cases in French Brittany.