138P - Exome sequencing analysis for the identification of actionable mutations related to neoadjuvant chemotherapy response in locally advanced breast cancer

Background

The goal of this study is to identify actionable mutations as predictive biomarkers to neoadjuvant chemotherapy response in patients with locally advanced breast cancer.

Methods

This study involved a cohort of 121 somatic exomes where quality analysis were made with tools as FastQC, MultiQC and FastQScreen, then we made an alignment to a reference genome using tools as Burrows-Wheeler-Aligner and Bowtie2, the next step consisted in the variant calling analysis using tools as Genome Analysis Toolkit and Freebayes in order to identify our interest mutations, finally we used BCtools to visualize the genetic variation we found, and we compared them in public databases as Genome in a Bottle and Platinum Genome in a Bottle. The second analysis was to do an CNV´s analysis in order to identify the correlation between gene expression and the presence of CNV´s.

Results

We found different variants related to the increasing of kinase activity in the PI3K pathway, these mutations were present in PIK3CA and were mainly represented by copy number amplifications and copy number losses. We also identified a correlation of CNV´s and the expression of the genes KCNJ3, PEX5L and RBM24. On the other hand we found genetic variations in RB1, ERBB2, NRAS, FGFR, EGFR which also were related to resistance to conventional therapy according to public databases.

Conclusions

Not only mutations in PIK3CA are related to trastuzumab resistance in locally advanced breast cancer patients but also are related to PIK3CA, AKT, PTEN signaling pathways. Added to this we found a correlation between the amount of CNV´s present and gene expression around an amount of genes.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

National Cancer Institute, Mexico City.

Funding

National Cancer Institute, Mexico City.

Disclosure

All authors have declared no conflicts of interest.