Differential TP73 exon usage in breast cancer molecular subtypes

GUERRERO GIMENEZ, MARTIN EDUARDO; CIOCCA, DANIEL RAMON; GOMEZ, LAURA; ZOPPINO, FELIPE CARLOS MARTIN; VARGAS ROIG, LAURA

Ciudad Autónoma de Buenos Aires

Conferencia; International Society for Computational Biology-Latin America Conference 2016; 2016

International Society for Computational Biology

Background: p73 protein is related to the p53 tumor protein which is structurally and functionally similar. The biology of p73 is complex since TP73 gene is transcribed into different isoforms that give rise to proteins with antagonistic properties, the transactivating isoforms (TAp73) that can act as tumor-suppressors and the DN-isoforms that behave as proto-oncogenes.Breast cancer (BC) is the leading type of cancer in women and it can be classified into five different subtypes with biological and clinical implications.The Cancer Genome Atlas (TCGA) BC study revealed frequent mutations of TP53 while mutations of TP73 were not found, however, the expression and splicing behaviour of TP73 in BC remains unclear. Here we examined the exon differential expression and usage of TP73 in the TCGA breast cancer RNASeq dataset using an EdgeR set of tools from the software R to grasp a better understanding of the TP73 complex role in BC biology and to elucidate the predominant isoforms expressed in the different subtypes.Results: This analysis shows a TP73 over-expression among all BC subtypes. Surprisingly, this up-regulation depends mostly on the over-expression of exons corresponding to the TAp73 specific domains. A significant suppression of the 4th exon was found in all subtypes which could imply a differential promoter usage of the gene favoring the TAp73 isofrom expression. Conclusion: To our knowledge this is the first description of an exon expression switch of this gene in BC. Our findings suggest a context dependent regulation of the TAp73 isoform in BC that should be further studied.