ABERRANT AND ALTERNATIVE SPLICING IN CANCER

Abstract

WORLDWIDE, GASTRIC CANCER IS ONE OF THE MOST COMMON CANCERS AND THE SECOND LEADING CAUSE OF CANCER DEATH. ALTERNATIVE SPLICING IS KNOWN TO SOMETIMES PLAY A ROLE IN CANCER IN GENERAL, AND SPECIFICALLY IN GASTRIC CANCER. HOWEVER, LITTLE IS KNOWN ABOUT THE FULL BREADTH OF THE EFFECTS OF ALTERNATIVE SPLICING IN GASTRIC TUMORIGENESIS. TO SYSTEMATICALLY INVESTIGATE THIS, THIS STUDY USED MASSIVELY PARALLEL NEXT GENERATION SEQUENCING TO SEQUENCE THE MRNA POPULATIONS OF (1) 12 GASTRIC ADENOCARCINOMAS AND MATCHED NON-MALIGNANT GASTRIC MUCOSA AND (2) 10 GASTRIC ADENOCARCINOMA CELL LINES. THE STUDY IDENTIFIED 320 GENES WITH LIKELY PRIVATE CANCER-ASSOCIATED SPLICEFORMS, AND FOUND THAT THESE GENES WERE SIGNIFICANTLY ENRICHED FOR FUNCTIONS RELATED TO CELL-CELL INTERACTION AND CYTOSKELETAL FUNCTION, THEMES THAT HAVE BEEN OBSERVED IN SPLICING CHANGES IN THE EPITHELIAL-MESENCHYMAL TRANSITION IN BREAST CANCERS. TO ASSESS THE GENERALITY OF THE ASSOCIATION OF SPLICEFORMS WITH GASTRIC CANCER, I ALSO USED RT