Feasibility of a novel non-invasive swab technique for serial whole-exome sequencing of cervical tumors during chemoradiation therapy

Background Clinically relevant genetic predictors of radiation response for cervical cancer are understudied due to the morbidity of repeat invasive biopsies required to obtain genetic material. Thus, we aimed to develop a novel noninvasive cervical swab technique to collect tumor DNA with adequate throughput to perform whole-exome sequencing (WES) at serial time points over the course of chemoradiation therapy (CRT). Methods Cervical cancer tumor samples from patients undergoing chemoradiation were collected at baseline, at week 1, week 3, and at the completion of CRT (week 5) using a noninvasive swab-based biopsy technique. Swab samples were analyzed with whole-exome sequencing (WES) with mutation calling using a custom pipeline optimized for shallow whole-exome sequencing with low tumor purity. Tumor mutation changes over the course of treatment were profiled. Results 217 samples were collected and successfully sequenced for 70 patients. A total of 33 patients had a complete set of samples at all four time points. The mean mapping rate was 98% for all samples, and the mean target coverage was 180. Overall mutation frequency decreased during CRT with disease response but mapping rate and mean target coverage remained at >98% and >180 reads at week 5. Conclusion This study demonstrates the feasibility and application of a noninvasive swab-based technique for WES analysis to investigate dynamic tumor mutational changes during treatment and may be a valuable approach to identify novel genes which confer radiation resistance.