Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients

Abstract

Growing efforts are being invested in investigating various molecular approaches to detect minimal residual disease (MRD) and predict disease recurrence. In our study, we investigated the utility of parallel longitudinal analysis of mutation and DNA methylation profiles for predicting MRD in postoperative non‐small‐cell lung cancer (NSCLC) patients. Tumor tissues and longitudinal blood samples were obtained from 65 patients with resected stage IA‐IIIB NSCLC. Somatic mutation and DNA methylation profiling were performed using ultra‐deep targeted sequencing and targeted bisulfite sequencing, respectively. Dynamic changes in plasma‐based mutation and tumor‐informed methylation profiles, reflected as MRD score, were observed from before surgery (baseline) to postoperative follow‐up, reflecting the decrease in tumor burden of the patients with resected NSCLC. Mutations were detected from plasma samples in 63% of the patients at baseline, which significantly reduced to 23‐25% during post‐operative follow‐ups. MRD score positive rate was 95.7% at baseline, which reduced to 74% at the first and 70% at the second follow‐up. Among the 5 relapsed patients with parallel longitudinal analysis of mutation and methylation profile, elevated MRD score was observed at follow‐up between 0.5‐7 months prior to radiologic recurrence for all 5 patients. Of them, 4 patients also had concomitant increase in allelic fraction of mutations in at least 1 follow‐up time point, but one patient had no mutation detected throughout all follow‐ups. Our results demonstrate that longitudinal profiling of mutation and DNA methylation may have potential for detecting MRD and predicting recurrence in postoperative NSCLC patients.

Dynamic monitoring of UBA1 somatic mutations in patients with relapsing polychondritis

“…Previous studies have reported low frequency [ 11 , 12 ] and dynamic changes [ 13 , 14 ] in somatic variants. Therefore, to our knowledge, we performed multiple ddPCR detections on 11 patients with RP using blood samples collected at different follow-up time points for the first time.…”

New biochemical, immune and molecular markers in lung cancer: Diagnostic and prognostic opportunities

“…84 Longitudinal methylation profiling along with somatic mutation analysis in patients with NSCLC have also shown prognostic potential in assessing the risk of recurrence. 85 With regard to its prognostic value, the level of ctDNA was found indicative of lymph node involvement in resectable NSCLC. 86 Other investigators collected tissue and plasma samples from NSCLC patients before and after surgery in order to identify driver mutations in genes, including EGFR, KRAS, TP53, BRAF, PIK3CA, and ERBB2.…”

Longitudinal prediction of DNA methylation to forecast epigenetic outcomes

“…Previous studies have demonstrated the power of longitudinal molecular pro ling in tracking tumour evolution and identifying therapeutic targets in cancer patients [1,2]. More recent investigation on population cohorts showcased how longitudinal molecular pro ling aided in predicting treatment outcomes and tailoring interventions for patients with chronic diseases [3,4]. However, when health outcomes are recorded, there may be a lack of biosamples available to measure the molecular changes occurring at that time.…”