TY - JOUR
T1 - Distribution of circulating tumor DNA in lung cancer
T2 - Analysis of the primary lung and bone marrow along with the pulmonary venous and peripheral blood
AU - Goto, Taichiro
AU - Hirotsu, Yosuke
AU - Amemiya, Kenji
AU - Nakagomi, Takahiro
AU - Shikata, Daichi
AU - Yokoyama, Yujiro
AU - Okimoto, Kenichiro
AU - Oyama, Toshio
AU - Mochizuki, Hitoshi
AU - Omata, Masao
N1 - Funding Information:
This study was supported by a Grant-in-Aid for Genome Research Project from Yamanashi Prefecture (YH and MO) and a grant from The YASUDA Medical Foundation (YH).
Publisher Copyright:
© Goto et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Circulating tumor DNA
KW - Distribution
KW - Lung cancer
KW - Next-generation sequencing
KW - Plasma
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U2 - 10.18632/oncotarget.19538
DO - 10.18632/oncotarget.19538
M3 - Article
AN - SCOPUS:85029059676
SN - 1949-2553
VL - 8
SP - 59268
EP - 59281
JO - Oncotarget
JF - Oncotarget
IS - 35
ER -
