TY - JOUR
T1 - Prognostic significance of circulating RET M918T mutated tumor DNA in patients with advanced medullary thyroid carcinoma
AU - Cote, Gilbert J.
AU - Evers, Caitlin
AU - Hu, Mimi I.
AU - Grubbs, Elizabeth G.
AU - Williams, Michelle D.
AU - Hai, Tao
AU - Duose, Dzifa Y.
AU - Houston, Michal R.
AU - Bui, Jacquelin H.
AU - Mehrotra, Meenakshi
AU - Waguespack, Steven G.
AU - Busaidy, Naifa L.
AU - Cabanillas, Maria E.
AU - Habra, Mouhammed Amir
AU - Luthra, Rajyalakshmi
AU - Sherman, Steven I.
N1 - Publisher Copyright:
Copyright © 2017 Endocrine Society.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2017-01039
DO - 10.1210/jc.2017-01039
M3 - Article
C2 - 28911154
AN - SCOPUS:85031093086
SN - 0021-972X
VL - 102
SP - 3591
EP - 3599
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -