Distribution of circulating tumor DNA in lung cancer: Analysis of the primary lung and bone marrow along with the pulmonary venous and peripheral blood

Taichiro Goto, Yosuke Hirotsu, Kenji Amemiya, Takahiro Nakagomi, Daichi Shikata, Yujiro Yokoyama, Kenichiro Okimoto, Toshio Oyama, Hitoshi Mochizuki, Masao Omata

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)59268-59281
Number of pages14
JournalOncotarget
Volume8
Issue number35
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • Circulating tumor DNA
  • Distribution
  • Lung cancer
  • Next-generation sequencing
  • Plasma

ASJC Scopus subject areas

  • Oncology

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    Goto, T., Hirotsu, Y., Amemiya, K., Nakagomi, T., Shikata, D., Yokoyama, Y., Okimoto, K., Oyama, T., Mochizuki, H., & Omata, M. (2017). Distribution of circulating tumor DNA in lung cancer: Analysis of the primary lung and bone marrow along with the pulmonary venous and peripheral blood. Oncotarget, 8(35), 59268-59281. https://doi.org/10.18632/oncotarget.19538