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Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non-small cell lung cancer patients.
- Source :
-
Cancer medicine [Cancer Med] 2021 Dec; Vol. 10 (23), pp. 8377-8386. Date of Electronic Publication: 2021 Oct 19. - Publication Year :
- 2021
-
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.<br /> (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Subjects :
- Adult
Aged
Biomarkers, Tumor genetics
Carcinoma, Non-Small-Cell Lung pathology
Carcinoma, Non-Small-Cell Lung surgery
Female
High-Throughput Nucleotide Sequencing
Humans
Longitudinal Studies
Lung Neoplasms pathology
Lung Neoplasms surgery
Male
Middle Aged
Mutation
Neoplasm Recurrence, Local
Neoplasm Staging
Neoplasm, Residual
Predictive Value of Tests
Prospective Studies
Risk Factors
Tumor Burden
Carcinoma, Non-Small-Cell Lung genetics
DNA Methylation
Lung Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-7634
- Volume :
- 10
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Cancer medicine
- Publication Type :
- Academic Journal
- Accession number :
- 34664796
- Full Text :
- https://doi.org/10.1002/cam4.4339