CLINICAL APPLICATION OF CANCER EXOME SEQUENCING

Abstract

In the present thesis, we first seek to identify new driver events in gastrointestinal stromal tumor (GIST), explore their molecular consequences and test their utility as prognostic markers. To this end, we performed whole-exome sequencing on 18 GIST tumor samples from 14 patients, followed by targeted sequencing of 3 candidate cancer genes from an independent 109 GIST samples. Statistical approach was employed in order to prioritize novel significantly mutated genes in the tumor cohort. We identified for the first time, recurrent SETD2 mutations in GIST samples. In the second part of this thesis, we seek to characterize the genetic landscape of cisplatin-treated squamous cell carcinoma of the head and neck (SCCHN) and identify potential predictive biomarkers for dacomitinib sensitivity. Whole exome sequencing was performed on 18 cisplatin-treated metastatic SCCHN tumors and their matched germline DNA. Somatic mutations in REV3L, the gene encoding the catalytic subunit of DNA polymerase ζ involved in translesional synthesis, are significantly enriched in a subset of patients who derived extended clinical benefit to dacomitinib.