Journal
ONCOTARGET
Volume 8, Issue 35, Pages 59268-59281Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19538
Keywords
circulating tumor DNA; distribution; lung cancer; next-generation sequencing; plasma
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Funding
- YASUDA Medical Foundation
- Yamanashi Prefecture
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Circulating tumor DNA (ctDNA), extracted from plasma, is a non-invasive surrogate biomarker. However, the distribution of ctDNA in the body still remains to be elucidated. In this study, resected lung tumors, with simultaneous blood and bone marrow samples, were analyzed to elucidate the distribution of ctDNA. Rib bone marrow, pulmonary venous blood (Pul. V) and peripheral blood (Peri. B) were obtained from 30 patients. The liquid samples were divided into cell pellets and supernatant by centrifugation; a total of 212 DNA samples were subjected to massively parallel sequencing. ctDNA was detected in 5 patients. Given that the frequency of mutations in the primary tumor was considered to be 100%, those in the other specimens were as follows; Pul. V plasma 20%, Peri. B plasma 11%, and the other samples 0%. Furthermore, ctDNA reflected the predominant mutations in the primary lesion. Clinically, the presence of ctDNA was associated with significantly poorer survival. These results suggest ctDNA spill over into an immediate outflow tract (Pul. V), and from there is disseminated to the entire body. Thus, it can be inferred that ctDNA reflects the cancer progression and could function as a prognostic marker.
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