Neurotrophic receptor tyrosine kinase family members in secretory and non-secretory breast carcinomas

Abstract

BACKGROUND Breast cancer is the most common female cancer and a major cause of morbidity and mortality. Progress in breast cancer therapeutics has been attained with the introduction of targeted therapies for specific sub-sets. However, other subsets lack targeted interventions and thus there is persisting need for identification and characterization of molecular targets in order to advance breast cancer therapeutics. AIM To analyze the role of lesions in neurotrophic receptor tyrosine kinase (NTRK) genes in breast cancers. METHODS Analysis of publicly available genomic breast cancer datasets was performed for identification and characterization of cases with fusions and other molecular abnormalities involving NTRK1 , NTRK2 and NTRK3 genes. RESULTS NTRK fusions are present in a small number of breast cancers at the extensive GENIE project data set which contains more than 10000 breast cancers. These cases are not identified as secretory in the database, suggesting that the histologic characterization is not always evident. In the breast cancer The Cancer Genome Atlas (TCGA) cohort the more common molecular lesion in NTRK genes is amplification of NTRK1 observed in 7.9% of breast cancers. CONCLUSION Neurotrophin receptors molecular lesions other than fusions are observed more often than fusions. However, currently available NTRK inhibitors are effective mainly for fusion lesions. Amplifications of NTRK1 , being more frequent in breast cancers, could be a viable therapeutic target if inhibitors efficacious for them become available.