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

被引：18

作者：

Goto, Taichiro ^{[1
]}

Hirotsu, Yosuke ^{[2
]}

Amemiya, Kenji ^{[2
]}

Nakagomi, Takahiro ^{[1
]}

Shikata, Daichi ^{[1
]}

Yokoyama, Yujiro ^{[1
]}

Okimoto, Kenichiro ^{[2
]}

Oyama, Toshio ^{[3
]}

Mochizuki, Hitoshi ^{[2
]}

Omata, Masao ^{[2
,4
]}

机构：

[1] Yamanashi Cent Hosp, Lung Canc & Resp Dis Ctr, Yamanashi, Japan

[2] Yamanashi Cent Hosp, Genome Anal Ctr, Yamanashi, Japan

[3] Yamanashi Cent Hosp, Dept Pathol, Yamanashi, Japan

[4] Univ Tokyo, Tokyo, Japan

来源：

ONCOTARGET | 2017年 / 8卷 / 35期

关键词：

circulating tumor DNA; distribution; lung cancer; next-generation sequencing; plasma; SQUAMOUS-CELL CARCINOMA; ACQUIRED-RESISTANCE; CLINICAL-SIGNIFICANCE; GERMLINE MUTATIONS; KRAS MUTATIONS; NUCLEIC-ACIDS; PLASMA; EGFR; ADENOCARCINOMA; RELEVANCE;

D O I：

10.18632/oncotarget.19538

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：59268 / 59281

页数：14

共 61 条

[1] Circulating Tumor Cells and Circulating Tumor DNA [J].

Alix-Panabieres, Catherine ;

Schwarzenbach, Heidi ;

Pantel, Klaus .

ANNUAL REVIEW OF MEDICINE, VOL 63, 2012, 63 :199-215

[2] Serum CA 19-9 as a Biomarker for Pancreatic Cancer-A Comprehensive Review [J].

Ballehaninna U.K. ;

Chamberlain R.S. .

Indian Journal of Surgical Oncology, 2011, 2 (2) :88-100

[3] Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].

Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

Fecher, Leslie A. ;

Gallia, Gary L. ;

Gibbs, Peter ;

Le, Dung ;

Giuntoli, Robert L. ;

Goggins, Michael ;

Hogarty, Michael D. ;

Holdhoff, Matthias ;

Hong, Seung-Mo ;

Jiao, Yuchen ;

Juhl, Hartmut H. ;

Kim, Jenny J. ;

Siravegna, Giulia ;

Laheru, Daniel A. ;

Lauricella, Calogero ;

Lim, Michael ;

Lipson, Evan J. ;

Marie, Suely Kazue Nagahashi ;

Netto, George J. ;

Oliner, Kelly S. ;

Olivi, Alessandro ;

Olsson, Louise ;

Riggins, Gregory J. ;

Sartore-Bianchi, Andrea ;

Schmidt, Kerstin ;

Shih, Ie-Ming ;

Oba-Shinjo, Sueli Mieko ;

Siena, Salvatore ;

Theodorescu, Dan ;

Tie, Jeanne ;

Harkins, Timothy T. ;

Veronese, Silvio ;

Wang, Tian-Li ;

Weingart, Jon D. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[4] Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer [J].

Board, Ruth E. ;

Wardley, Andrew M. ;

Dixon, J. Michael ;

Armstrong, Anne C. ;

Howell, Sacha ;

Renshaw, Lorna ;

Donald, Emma ;

Greystoke, Alastair ;

Ranson, Malcolm ;

Hughes, Andrew ;

Dive, Caroline .

BREAST CANCER RESEARCH AND TREATMENT, 2010, 120 (02) :461-467

[5] Circulating DNA in diagnosis and monitoring EGFR gene mutations in advanced non-small cell lung cancer [J].

Bordi, Paola ;

Del Re, Marzia ;

Danesi, Romano ;

Tiseo, Marcello .

TRANSLATIONAL LUNG CANCER RESEARCH, 2015, 4 (05) :584-597

[6] Comprehensive molecular profiling of lung adenocarcinoma [J].

Collisson, Eric A. ;

Campbell, Joshua D. ;

Brooks, Angela N. ;

Berger, Alice H. ;

Lee, William ;

Chmielecki, Juliann ;

Beer, David G. ;

Cope, Leslie ;

Creighton, Chad J. ;

Danilova, Ludmila ;

Ding, Li ;

Getz, Gad ;

Hammerman, Peter S. ;

Hayes, D. Neil ;

Hernandez, Bryan ;

Herman, James G. ;

Heymach, John V. ;

Jurisica, Igor ;

Kucherlapati, Raju ;

Kwiatkowski, David ;

Ladanyi, Marc ;

Robertson, Gordon ;

Schultz, Nikolaus ;

Shen, Ronglai ;

Sinha, Rileen ;

Sougnez, Carrie ;

Tsao, Ming-Sound ;

Travis, William D. ;

Weinstein, John N. ;

Wigle, Dennis A. ;

Wilkerson, Matthew D. ;

Chu, Andy ;

Cherniack, Andrew D. ;

Hadjipanayis, Angela ;

Rosenberg, Mara ;

Weisenberger, Daniel J. ;

Laird, Peter W. ;

Radenbaugh, Amie ;

Ma, Singer ;

Stuart, Joshua M. ;

Byers, Lauren Averett ;

Baylin, Stephen B. ;

Govindan, Ramaswamy ;

Meyerson, Matthew ;

Rosenberg, Mara ;

Gabriel, Stacey B. ;

Cibulskis, Kristian ;

Sougnez, Carrie ;

Kim, Jaegil ;

Stewart, Chip .

NATURE, 2014, 511 (7511) :543-550

[7] Liquid biopsy: monitoring cancer-genetics in the blood [J].

Crowley, Emily ;

Di Nicolantonio, Federica ;

Loupakis, Fotios ;

Bardelli, Alberto .

NATURE REVIEWS CLINICAL ONCOLOGY, 2013, 10 (08) :472-484

[8] Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer [J].

Dawson, Sarah-Jane ;

Tsui, Dana W. Y. ;

Murtaza, Muhammed ;

Biggs, Heather ;

Rueda, Oscar M. ;

Chin, Suet-Feung ;

Dunning, Mark J. ;

Gale, Davina ;

Forshew, Tim ;

Mahler-Araujo, Betania ;

Rajan, Sabrina ;

Humphray, Sean ;

Becq, Jennifer ;

Halsall, David ;

Wallis, Matthew ;

Bentley, David ;

Caldas, Carlos ;

Rosenfeld, Nitzan .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (13) :1199-1209

[9] The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers [J].

Diaz, Luis A., Jr. ;

Williams, Richard T. ;

Wu, Jian ;

Kinde, Isaac ;

Hecht, J. Randolph ;

Berlin, Jordan ;

Allen, Benjamin ;

Bozic, Ivana ;

Reiter, Johannes G. ;

Nowak, Martin A. ;

Kinzler, Kenneth W. ;

Oliner, Kelly S. ;

Vogelstein, Bert .

NATURE, 2012, 486 (7404) :537-540

[10] Circulating mutant DNA to assess tumor dynamics [J].

Diehl, Frank ;

Schmidt, Kerstin ;

Choti, Michael A. ;

Romans, Katharine ;

Goodman, Steven ;

Li, Meng ;

Thornton, Katherine ;

Agrawal, Nishant ;

Sokoll, Lori ;

Szabo, Steve A. ;

Kinzler, Kenneth W. ;

Vogelstein, Bert ;

Diaz, Luis A., Jr. .

NATURE MEDICINE, 2008, 14 (09) :985-990

← 1 2 3 4 5 6 7 →