Somatic mutations in leukocytes infiltrating primary breast cancers

• DOI: 10.1038/npjbcancer.2015.5
• Publication Date: 2015-06-10T14:26:29Z
• Authors: Maria Kleppe; Elizabeth Comen; Hannah Y Wen; Lennart Bastian; Brian Blum; Franck T Rapaport; Matthew Keller; Zvika Granot; Nicolas Socci; Agnès Viale; Daoqi You; Robert Benezra; Britta Weigelt; Edi Brogi; Michael F Berger; Jorge S Reis-Filho; Ross L Levine; Larry Norton
• Keywords: Exome

Malignant transformation requires the interaction of cancer cells with their microenvironment, including infiltrating leukocytes. However, somatic mutational studies have focused on alterations in cells, assuming that microenvironment is genetically normal. Because we hypothesized this might not be a valid assumption, performed exome sequencing and targeted to investigate for presence pathogenic mutations tumor-associated leukocytes breast cancers.We used evaluate sorted tumor-infiltrating CD45-positive from primary untreated cancers. We high-depth determine presence/absence identified cancer-infiltrating purified tumor circulating blood cells.Capture-based 15 paired matched germline DNA variants known genes all patients our cohort. validated by through orthogonal sequencing. Ten harbored previously reported as somatically acquired variants, leukemia (DNTM3A, TET2, BCOR). One observed was also detected same at lower allele frequency than cells.Here show mutations, genes, are present subset This observation allows possibility interact mutant leukocytes, which has many potential clinical implications.