1. Prognostic Significance of Circulating RET M918T Mutated Tumor DNA in Patients With Advanced Medullary Thyroid Carcinoma
- Author
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Jacquelin H. Bui, Steven I. Sherman, Gilbert J. Cote, Mouhammed Amir Habra, Steven G. Waguespack, Elizabeth G. Grubbs, Michal R. Houston, Rajyalakshmi Luthra, Mimi I. Hu, Tao Hai, Meenakshi Mehrotra, Dzifa Y. Duose, Maria E. Cabanillas, Naifa L. Busaidy, Michelle D. Williams, and Caitlin Evers
- Subjects
Male ,0301 basic medicine ,Oncology ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,DNA Mutational Analysis ,Clinical Biochemistry ,Polymerase Chain Reaction ,Biochemistry ,Cohort Studies ,0302 clinical medicine ,Endocrinology ,medicine.diagnostic_test ,Biopsy, Needle ,DNA, Neoplasm ,Middle Aged ,Prognosis ,humanities ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Female ,Adult ,medicine.medical_specialty ,Context (language use) ,Risk Assessment ,Disease-Free Survival ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,Biopsy ,Carcinoma ,medicine ,Humans ,Neoplasm Invasiveness ,Thyroid Neoplasms ,Liquid biopsy ,Clinical Research Articles ,Survival analysis ,Aged ,Neoplasm Staging ,business.industry ,Calcitonin Measurement ,Proto-Oncogene Proteins c-ret ,Biochemistry (medical) ,medicine.disease ,Survival Analysis ,Carcinoma, Neuroendocrine ,030104 developmental biology ,Calcitonin ,business - Abstract
Context Interpretation of calcitonin measurement to predict the prognosis of medullary thyroid carcinoma (MTC) requires multiple measurements over an extended time period, making it an imperfect biomarker for evaluating prognosis or disease behavior. Single circulating cell-free DNA (cfDNA) values have been shown to be a valuable prognostic marker for several solid tumors. Objective We tested the hypothesis that cfDNA containing the RET M918T mutation could be detected in the blood of patients with advanced MTC whose tumor harbored an M918T mutation and would be able to predict overall survival more reliably than calcitonin. Design The level of cfDNA containing RET M918T mutation was measured in the plasma of patients with MTC via droplet digital polymerase chain reaction. Patients Patients had a confirmed sporadic MTC diagnosis, a serum calcitonin measurement >100 pg/mL, and tumor tissue biopsy results providing RET M918T mutation status. There were 75 patients included in this study, 50 of whom harbored an RET M918T mutation by tissue biopsy. Results RET M918T cfDNA was detected in 16 of 50 patients (32%) with a positive tissue biopsy. The detection of RET M918T cfDNA strongly correlated with worse overall survival and more accurately predicted a worse outcome than calcitonin doubling time. Conclusions Liquid biopsy is able to detect RET M918T mutations in patient plasma with high specificity but low sensitivity. In patients with established somatic RET M918T mutations, the allelic fraction of circulating tumor DNA is prognostic for overall survival and may play a role in monitoring response to treatment.
- Published
- 2017