CHARACTERIZATION OF IMMUNE-RELATED GENE EXPRESSION IN THE TUMOR MICROENVIRONMENT OF TRIPLE NEGATIVE BREAST CANCERS

Breast Cancer (BC) is a heterogeneous disease. Triple negative breast cancers (TNBC) are an aggressive subtype accounting for 20% of all BC. Notaby, treatment options for TNBC are limited due to the lack of suitable targets. Thus, this study aimed to explore the tumor microenvironment (TME) in TNBC to assess how it may influence the patients’ pathological response (PR) to treatments. To achieve that, in-silico prediction was performed to assess how differential expression of immune-related genes impacts the Progression Free Interval (PFI) and Overall Survival (OS), obtaining long-term outcome information. The UCSC Xena database was used to analyze the association between immune-related gene expression and OS or PFI. GEPIA2 was used to retrieve information on gene-specific cancer OS. As for the experimental lab validation, Next Generation Sequencing analysis was performed to assess the possible link between the TME and different PR to neoadjuvant chemothrapy, obtaining short-term outcome information. 20 FFPE biopsies specimens were retrospectively selected for this study. Cases have been classified in 2 groups: (i) “pCR”, composed of 11 patients who achieved a complete PR; (ii) “pPR”, including 9 patients who achieved a partial or absent PR. RNA was extracted and the AmpliSeq for Illumina Immune Response Panel was used to investigate 399 genes involved in TME and immune response system. Adequate statistical analyses were applied to evaluate differences between groups

Human rDNA copy number is unstable in metastatic breast cancers

Chromatin-mediated silencing, including the formation of heterochromatin, silent chromosome territories, and repressed gene promoters, acts to stabilize patterns of gene regulation and the physical structure of the genome. Reduction of chromatin-mediated silencing can result in genome rearrangements, particularly at intrinsically unstable regions of the genome such as transposons, satellite repeats, and repetitive gene clusters including the rRNA gene clusters (rDNA). It is thus expected that mutational or environmental conditions that compromise heterochromatin function might cause genome instability, and diseases associated with decreased epigenetic stability might exhibit genome changes as part of their aetiology. We find the support of this hypothesis in invasive ductal breast carcinoma, in which reduced epigenetic silencing has been previously described, by using a facile method to quantify rDNA copy number in biopsied breast tumours and pair-matched healthy tissue. We found that rDNA and satellite DNA sequences had significant copy number variation - both losses and gains of copies - compared to healthy tissue, arguing that these genome rearrangements are common in developing breast cancer. Thus, any proposed aetiology onset or progression of breast cancer should consider alterations to the epigenome, but must also accommodate concomitant changes to genome sequence at heterochromatic loci.NIH [GM123640]12 month embargo; published online: 12 August 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]