Feasibility of a novel non-invasive swab technique for serial whole-exome sequencing of cervical tumors during chemoradiation therapy
Feasibility of a novel non-invasive swab technique for serial whole-exome sequencing of cervical tumors during chemoradiation therapy
Abstract BackgroundClinically 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). MethodsCervical 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. Results217 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. ConclusionThis 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.
Wang Rui、Bronk Julianna K.、Wu Xiaogang、Chapman Bhavana V.、Karpinets Tatiana V.、Song Xingzhi、Zhang Jianhua、Colbert Lauren E.、Futreal Andrew M.、Kapadia Chiraag、Klopp Ann H.
Department of Radiation Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center||Department of Molecular and Cellular Biology, Baylor College of MedicineDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center
医学研究方法肿瘤学妇产科学
cervical cancerchemoradiationwhole exome sequencingnoninvasive biopsy
Wang Rui,Bronk Julianna K.,Wu Xiaogang,Chapman Bhavana V.,Karpinets Tatiana V.,Song Xingzhi,Zhang Jianhua,Colbert Lauren E.,Futreal Andrew M.,Kapadia Chiraag,Klopp Ann H..Feasibility of a novel non-invasive swab technique for serial whole-exome sequencing of cervical tumors during chemoradiation therapy[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2022.02.23.22271256.点此复制
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