Comprehensive analysis of ALK, ROS1 and RET rearrangements in locally advanced rectal cancer

ABSTRACT

Gene rearrangements, such as anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1), rearranged during transfection (RET) and neurotrophic receptor tyrosine kinase 1 (NTRK1), identified in cancer have been indicated to be robust therapeutic targets in lung carcinomas. However, a few studies have focussed on locally advanced rectal cancer (LARC). The discovery of novel gene fusions is also valuable for LARC research. We used mass spectrometry-based assays and RNA sequencing to detect both known ALK, ROS1, RET and NTRK1 rearrangements and novel gene fusions in LARC patients. FusionMap was also used to find gene fusions. None of the ALK, ROS1, RET or NTRK1 gene fusions were detected by mass spectrometry-based assays or RNA sequencing. Three fusion candidates, integrin subunit beta 7 (ITGB7)-ROS1, lamin A/C (LMNA)-NTRK1 and Golgi-associated PDZ and coiled-coil motif containing (GOPC)-keratin 8 (KRT8), showed relatively high junction-spanning reads by the FusionMap algorithm, but did not pass validation. These results suggest that no ALK, ROS1 or RET rearrangements were found in LARC.