DNA-junction-based personalized liquid biopsy assays could inform management of aggressive endometrial cancer.
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Harris Faye R, De Vitis Luigi A, Grcevich Leah, Capasso Ilaria, Murphy Stephen J, Smadbeck James B, McCune Alexa F, Ali Mohamed F, Karagouga Giannoula, Johnson Sarah H, Sadeghian Dorsay, Schivardi Gabriella, Cucinella Giuseppe, Reynolds Evelyn A, Choong Grace M, Yang Lin, Larish Alyssa M, Barrett Michael T, Emanuel Angela R, Schaefer-Klein Janet L, Kosari Farhad, Penheiter Alan R, Grassi Tommaso, Sotiriou Sotiris, Cheville John, Feathers Ryan W, Lin Wan-Hsin, Lemens Maureen, Borad Mitesh J, Mansfield Aaron S, Fought Angela J, McGree Michaela E, Anastasiadis Panos Z, Weroha S John, Mariani Andrea, Vasmatzis George
Аннотация
METHODS: Whole genome sequencing tumor data was analyzed from 36 patients to select prominent somatic tumor-specific DNA junctions. Personalized quantitative polymerase chain reaction assays were developed for each junction and applied to available blood specimens to measure levels of ctDNA.
RESULTS: Pre-surgical blood ctDNA was detected in 71% of the cases tested (56% early-stage vs 88% advanced-stage). In patients with available pre-amplified pre-surgical ctDNA (n = 15), pre-surgical ctDNA levels were elevated in patients with vital status or "alive with disease" or "died of disease" compared to patients with "no evidence of disease" (p < .005). Among 17 patients followed serially, ctDNA detection preceded clinical detection of recurrence in 5 of 8 cases and was concurrent in 1, with the caveat that imaging was rarely concurrent with blood draw timing.
CONCLUSIONS: Personalized junction-based measurement of ctDNA demonstrated promising clinical validity in pre-surgical prognosis and relapse prediction.