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

doi:10.18632/oncotarget.19538

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Research Papers:

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 and Masao Omata

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Oncotarget. 2017; 8:59268-59281. https://doi.org/10.18632/oncotarget.19538

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Abstract

Taichiro Goto1,*, Yosuke Hirotsu2,*, Kenji Amemiya2, Takahiro Nakagomi1, Daichi Shikata1, Yujiro Yokoyama1, Kenichiro Okimoto2, Toshio Oyama3, Hitoshi Mochizuki2 and Masao Omata2,4

1Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Yamanashi, Japan

2Genome Analysis Center, Yamanashi Central Hospital, Yamanashi, Japan

3Department of Pathology, Yamanashi Central Hospital, Yamanashi, Japan

4University of Tokyo, Tokyo, Japan

*Taichiro Goto and Yosuke Hirotsu contributed equally to this study

Correspondence to:

Taichiro Goto, email: [email protected]

Keywords: circulating tumor DNA, distribution, lung cancer, next-generation sequencing, plasma

Received: October 19, 2016 Accepted: June 02, 2017 Published: July 25, 2017

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.

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Research Papers:

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

Abstract