{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:04:37Z","timestamp":1793639077605,"version":"4.5.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Cell-free DNA circulating in blood is a candidate biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic nondiseased cells, DNA released from dead cancer cells varies in size. We developed a novel method to measure the ratio of longer to shorter DNA fragments (DNA integrity) in serum as a potential biomarker for patients with colorectal cancer (CRC) or periampullary cancers (PACs).<\/jats:p>\n                  <jats:p>Methods: Sera from 32 patients with CRC (3 stage I, 14 stage II, 6 stage III, and 9 stage IV patients), 19 patients with PACs (2 stage I, 9 stage II, 1 stage III, and 7 stage IV patients), and 51 healthy volunteers were assessed by quantitative real-time PCR of ALU repeats (ALU-qPCR) with 2 sets of primers (115 and 247 bp) amplifying different lengths of DNA. We used serum directly as a template for ALU-qPCR without DNA purification. DNA integrity was determined as ratio of qPCR results of 247-bp ALU over 115-bp ALU.<\/jats:p>\n                  <jats:p>Results: ALU-qPCR had a detection limit of 0.01 pg of DNA. Eliminating DNA purification reduced technical artifacts and reagent\/labor costs. Serum DNA integrity was significantly increased for stage I\/II and III\/IV CRC and stage I\/II and III\/IV PACs (P = 0.002, P = 0.006, P = 0.022, and P &amp;lt;0.0001, respectively). ROC curves for detecting CRC and PACs had areas under the curves of 0.78 and 0.80, respectively.<\/jats:p>\n                  <jats:p>Conclusions: Direct ALU-qPCR is a robust, highly sensitive, and high-throughput method to measure serum DNA integrity. DNA integrity is a potential serum biomarker for detection and evaluation of CRC and PACs.<\/jats:p>","DOI":"10.1373\/clinchem.2006.068577","type":"journal-article","created":{"date-parts":[[2006,5,24]],"date-time":"2006-05-24T20:22:14Z","timestamp":1148502134000},"page":"1062-1069","source":"Crossref","is-referenced-by-count":293,"title":["Increased Integrity of Free Circulating DNA in Sera of Patients with Colorectal or Periampullary Cancer: Direct Quantitative PCR for ALU Repeats"],"prefix":"10.1093","volume":"52","author":[{"given":"Naoyuki","family":"Umetani","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology and Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology and Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA"},{"name":"Department of Molecular Oncology and Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Hiramatsu","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology and Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard A","family":"Reber","sequence":"first","affiliation":[{"name":"Section of Gastrointestinal Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar J","family":"Hines","sequence":"first","affiliation":[{"name":"Section of Gastrointestinal Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton J","family":"Bilchik","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology and Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave S B","family":"Hoon","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology and Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,6,1]]},"reference":[{"key":"2020022801325754800_R1","doi-asserted-by":"crossref","unstructured":"Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA Cancer J Clin2005;55:10-30.","DOI":"10.3322\/canjclin.55.1.10"},{"key":"2020022801325754800_R2","doi-asserted-by":"crossref","unstructured":"Frebourg T, Bercoff E, Manchon N, Senant J, Basuyau JP, Breton P, et al. The evaluation of CA 19-9 antigen level in the early detection of pancreatic cancer: a prospective study of 866 patients. Cancer1988;62:2287-2290.","DOI":"10.1002\/1097-0142(19881201)62:11<2287::AID-CNCR2820621103>3.0.CO;2-H"},{"key":"2020022801325754800_R3","doi-asserted-by":"crossref","unstructured":"Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful?. Clin Chem2001;47:624-630.","DOI":"10.1093\/clinchem\/47.4.624"},{"key":"2020022801325754800_R4","doi-asserted-by":"crossref","unstructured":"Taback B, Hoon DS. Circulating nucleic acids and proteomics of plasma\/serum: clinical utility. Ann N Y Acad Sci2004;1022:1-8.","DOI":"10.1196\/annals.1318.002"},{"key":"2020022801325754800_R5","unstructured":"Taback B, Hoon DS. Circulating nucleic acids in plasma and serum: past, present and future. Curr Opin Mol Ther2004;6:273-278."},{"key":"2020022801325754800_R6","doi-asserted-by":"crossref","unstructured":"Fujimoto A, O\u2019Day SJ, Taback B, Elashoff D, Hoon DS. Allelic imbalance on 12q22-23 in serum circulating DNA of melanoma patients predicts disease outcome. Cancer Res2004;64:4085-4088.","DOI":"10.1158\/0008-5472.CAN-04-0957"},{"key":"2020022801325754800_R7","unstructured":"Wang BG, Huang HY, Chen YC, Bristow RE, Kassauei K, Cheng CC, et al. Increased plasma DNA integrity in cancer patients. Cancer Res2003;63:3966-3968."},{"key":"2020022801325754800_R8","doi-asserted-by":"crossref","unstructured":"Giacona MB, Ruben GC, Iczkowski KA, Roos TB, Porter DM, Sorenson GD. Cell-free DNA in human blood plasma: length measurements in patients with pancreatic cancer and healthy controls. Pancreas1998;17:89-97.","DOI":"10.1097\/00006676-199807000-00012"},{"key":"2020022801325754800_R9","unstructured":"Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res2001;61:1659-1665."},{"key":"2020022801325754800_R10","doi-asserted-by":"crossref","unstructured":"Hwu HR, Roberts JW, Davidson EH, Britten RJ. Insertion and\/or deletion of many repeated DNA sequences in human and higher ape evolution. Proc Natl Acad Sci U S A1986;83:3875-3879.","DOI":"10.1073\/pnas.83.11.3875"},{"key":"2020022801325754800_R11","doi-asserted-by":"crossref","unstructured":"Gu Z, Wang H, Nekrutenko A, Li WH. Densities, length proportions, and other distributional features of repetitive sequences in the human genome estimated from 430 megabases of genomic sequence. Gene2000;259:81-88.","DOI":"10.1016\/S0378-1119(00)00434-0"},{"key":"2020022801325754800_R12","doi-asserted-by":"crossref","unstructured":"Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature2001;409:860-921.","DOI":"10.1038\/35057062"},{"key":"2020022801325754800_R13","doi-asserted-by":"crossref","unstructured":"Smit AF. The origin of interspersed repeats in the human genome. Curr Opin Genet Dev1996;6:743-748.","DOI":"10.1016\/S0959-437X(96)80030-X"},{"key":"2020022801325754800_R14","doi-asserted-by":"crossref","unstructured":"Jurka J. Repeats in genomic DNA: mining and meaning. Curr Opin Struct Biol1998;8:333-337.","DOI":"10.1016\/S0959-440X(98)80067-5"},{"key":"2020022801325754800_R15","doi-asserted-by":"crossref","unstructured":"Sorenson GD. Detection of mutated KRAS2 sequences as tumor markers in plasma\/serum of patients with gastrointestinal cancer. Clin Cancer Res2000;6:2129-2137.","DOI":"10.1111\/j.1749-6632.2000.tb06582.x"},{"key":"2020022801325754800_R16","doi-asserted-by":"crossref","unstructured":"Uemura T, Hibi K, Kaneko T, Takeda S, Inoue S, Okochi O, et al. Detection of K-ras mutations in the plasma DNA of pancreatic cancer patients. J Gastroenterol2004;39:56-60.","DOI":"10.1007\/s00535-003-1245-1"},{"key":"2020022801325754800_R17","unstructured":"Lindforss U, Zetterquist H, Papadogiannakis N, Olivecrona H. Persistence of K-ras mutations in plasma after colorectal tumor resection. Anticancer Res2005;25:657-661."},{"key":"2020022801325754800_R18","unstructured":"Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res1977;37:646-650."},{"key":"2020022801325754800_R19","doi-asserted-by":"crossref","unstructured":"Anker P, Mulcahy H, Chen XQ, Stroun M. Detection of circulating tumour DNA in the blood (plasma\/serum) of cancer patients. Cancer Metastasis Rev1999;18:65-73.","DOI":"10.1023\/A:1006260319913"},{"key":"2020022801325754800_R20","doi-asserted-by":"crossref","unstructured":"Holdenrieder S, Stieber P, von Pawel J, Raith H, Nagel D, Feldmann K, et al. Circulating nucleosomes predict the response to chemotherapy in patients with advanced non-small cell lung cancer. Clin Cancer Res2004;10:5981-5987.","DOI":"10.1158\/1078-0432.CCR-04-0625"},{"key":"2020022801325754800_R21","doi-asserted-by":"crossref","unstructured":"Herrera LJ, Raja S, Gooding WE, El-Hefnawy T, Kelly L, Luketich JD, et al. Quantitative analysis of circulating plasma DNA as a tumor marker in thoracic malignancies. Clin Chem2005;51:113-118.","DOI":"10.1373\/clinchem.2004.039263"},{"key":"2020022801325754800_R22","doi-asserted-by":"crossref","unstructured":"Taback B, O\u2019Day SJ, Hoon DS. Quantification of circulating DNA in the plasma and serum of cancer patients. Ann N Y Acad Sci2004;1022:17-24.","DOI":"10.1196\/annals.1318.004"},{"key":"2020022801325754800_R23","doi-asserted-by":"crossref","unstructured":"Holdenrieder S, Stieber P, Chan LY, Geiger S, Kremer A, Nagel D, et al. Cell-free DNA in serum and plasma: comparison of ELISA and quantitative PCR. Clin Chem2005;51:1544-1546.","DOI":"10.1373\/clinchem.2005.049320"},{"key":"2020022801325754800_R24","doi-asserted-by":"crossref","unstructured":"Umetani N, Hiramatsu S, Hoon DSB. Higher amount of free circulating DNA in serum than in plasma is not mainly caused by contaminated extraneous DNA during separation. CNAPSIV. Ann N Y Acad Sci 2006;in press..","DOI":"10.1196\/annals.1368.040"},{"key":"2020022801325754800_R25","doi-asserted-by":"crossref","unstructured":"Lam NY, Rainer TH, Chan LY, Joynt GM, Lo YMD. Time course of early and late changes in plasma DNA in trauma patients. Clin Chem2003;49:1286-1291.","DOI":"10.1373\/49.8.1286"},{"key":"2020022801325754800_R26","doi-asserted-by":"crossref","unstructured":"Chan KC, Zhang J, Hui AB, Wong N, Lau TK, Leung TN, et al. Size distributions of maternal and fetal DNA in maternal plasma. Clin Chem2004;50:88-92.","DOI":"10.1373\/clinchem.2003.024893"},{"key":"2020022801325754800_R27","doi-asserted-by":"crossref","unstructured":"Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale\u2014update based on new evidence. Gastroenterology2003;124:544-560.","DOI":"10.1053\/gast.2003.50044"},{"key":"2020022801325754800_R28","doi-asserted-by":"crossref","unstructured":"Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med1993;328:1365-1371.","DOI":"10.1056\/NEJM199305133281901"},{"key":"2020022801325754800_R29","doi-asserted-by":"crossref","unstructured":"Graham RA, Wang S, Catalano PJ, Haller DG. Postsurgical surveillance of colon cancer: preliminary cost analysis of physician examination, carcinoembryonic antigen testing, chest x-ray, and colonoscopy. Ann Surg1998;228:59-63.","DOI":"10.1097\/00000658-199807000-00009"},{"key":"2020022801325754800_R30","doi-asserted-by":"crossref","unstructured":"Griffin JF, Smalley SR, Jewell W, Paradelo JC, Reymond RD, Hassanein RE, et al. Patterns of failure after curative resection of pancreatic carcinoma. Cancer1990;66:56-61.","DOI":"10.1002\/1097-0142(19900701)66:1<56::AID-CNCR2820660112>3.0.CO;2-6"},{"key":"2020022801325754800_R31","unstructured":"Westerdahl J, Andren-Sandberg A, Ihse I. Recurrence of exocrine pancreatic cancer\u2013local or hepatic?. Hepatogastroenterology1993;40:384-387."}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/52\/6\/1062\/32686512\/clinchem1062.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/52\/6\/1062\/32686512\/clinchem1062.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T09:31:24Z","timestamp":1707039084000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/52\/6\/1062\/5627032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6,1]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2006,6,1]]},"published-print":{"date-parts":[[2006,6,1]]}},"URL":"https:\/\/doi.org\/10.1373\/clinchem.2006.068577","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2006,6,1]]},"published":{"date-parts":[[2006,6,1]]}}}