TY - JOUR T1 - Dynamic evolution of cervical cancer mutations during chemoradiation using novel sampling approach JF - bioRxiv DO - 10.1101/850388 SP - 850388 AU - Bhavana V. Chapman AU - Tatiana Karpinets AU - Travis T. Sims AU - Greyson Biegert AU - Xiaogang Wu AU - Andrea Y. Delgado Medrano AU - Patricia J. Eifel AU - Anuja Jhingran AU - Lilie L. Lin AU - Lois M. Ramondetta AU - Andrew M. Futreal AU - Amir A. Jazaeri AU - Michael Frumovitz AU - Kathleen M. Schmeler AU - Jingyan Yue AU - Aparna Mitra AU - Kyoko Yoshida-Court AU - Travis Solley AU - Geena Mathew AU - Mustapha Ahmed-Kaddar AU - Jianhua Zhang AU - Ann H. Klopp AU - Lauren E. Colbert Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/25/850388.abstract N2 - Objective The aim of this study was to validate a whole exome sequencing approach to longitudinally characterize the tumor mutational profile of cervical cancer patients undergoing chemoradiation (CRT).Experimental Design Cervical cancer tumor specimens from twenty-seven patients undergoing chemoradiation were collected before and throughout CRT and whole exome sequencing (WES) was performed to characterize individual mutations and alterations in unique genes. WES data were analyzed from cervical cancer patients in The Cancer Genome Atlas (TCGA) as a comparison group.Results Over 93% of mutated genes detected at baseline were present in TCGA. Tumor purity from collected swabs correlated with MRI tumor volumes during the course of treatment (R2=0.969). CDK4/CDK6/cyclin D1-related gene mutations involved in the ERK1/2, p16INK4, and p53 pathway and G1/S checkpoint most commonly persisted at the end of CRT.Conclusion This non-invasive swab technique to serially sample tumor during CRT will allow new discoveries of dynamic tumor mutational profile changes during chemoradiation for mucosal tumors. Mutations that survived or increased during the initial weeks of radiation treatment are potential drivers of radiation resistance including the CDL4/CDK6/cyclin D1-related pathway.Statement of Translational Relevance There are no established biomarkers to predict chemoradiation (CRT) response for cervical cancer patients. Serial biopsies cannot be performed due to risks of bleeding and fistula. We used a novel non-invasive swab-based biopsy technique to obtain serial samples from a cohort of twenty-seven patients through the course of treatment, and validated this approach to obtain whole exome sequencing data. We analyzed dynamic tumor mutation profiles during CRT. Results from this study show that mutations in CDK4/CDK6/cyclin D1-related genes increased at the end of CRT, suggesting this pathway as a potential driver of radiation resistance. ER -