P24: Genome doubling shapes the evolution and prognosis of advanced head and neck cancer

Introduction: Clear cell carcinoma (CCC) is a rare low-grade tumor of minor salivary gland origin with an EWSR1-ATF1 sequence. Pathologically, tumor cells have clear cytoplasm on a background of hyalinized stroma. Pathologically, the tumor cells have clear cytoplasm against a background of hyalinized stroma. We performed genomic analysis of five HGT cases with abnormal morphology and recurrent recurrence of CCC, including two atypical clear cell morphologies, and a search for novel partner genes.


Methods: In this study, we performed a histopathological and genomic analysis of five cases of CCC including two atypical subtypes—a case of “high-grade transformation” and “possessing a novel partner gene for EWSR1.” We performed a sequential analysis of the primary and recurrent tumor by whole-exome sequencing, RNA sequencing, Sanger sequencing, and fluorescence in situ hybridization (FISH) to investigate the effect of genomic changes on histopathology and clinical prognosis.


Results: A fusion gene involving the EWSR1 gene was detected in all cases. Four cases, including the “high-grade transformation,” harbored a known EWSR1-ATF1 fusion gene; however, one case harbored a novel EWSR1-LARP4 fusion gene. According to whole-exome sequencing and FISH analysis, the “high-grade transformation” and poor prognosis were caused by whole-genome doubling and subsequent genomic aberrations


Conclusions: We performed a detailed molecular genetic analysis of five cases of CCC. As a result, we identified a novel partner gene for EWSR1, LARP4, in indolent CCC. Importantly, HGT and poor prognosis were caused by whole genome doubling and subsequent genomic aberrations.