Cell‐free DNA and RNA in Plasma as a New Molecular Marker for Prostate and Breast Cancer

Papadopoulou, Eirini; E, Davilas; Sotiriou, Vasilios; Georgakopoulos, Eleftherios; Georgakopoulou, Stavroula; Koliopanos, Alexander; Aggelakis, Filipos; Dardoufas, K.; Agnanti, Niki; Karydas, I.; Nasioulas, Georgios

doi:10.1196/annals.1368.032

Cited by 104 publications

(64 citation statements)

References 14 publications

(30 reference statements)

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“…Circulating DNA has proven clinical utilities such as diagnosis and prognostication in various cancers including nasopharyngeal carcinoma, 17 lymphoma, 18 breast cancer, 19,20 and colorectal cancer. 21 This study is the first to report the detection of circulating DNA harboring the BRAF mutation for patients with PTC.…”

Section: Discussionmentioning

confidence: 99%

Detectable BRAF mutation in serum DNA samples from patients with papillary thyroid carcinomas

Chuang

Poeta

et al. 2009

Head & Neck

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BACKGROUND.: An activating point mutation of the BRAF oncogene results in a V600E amino acid missense mutation found in a majority of papillary thyroid carcinomas (PTC). METHODS.: In this study, 28 matched tumor and serum samples obtained from patients with both benign and malignant thyroid disorders were analyzed for BRAF mutation using a gap-ligase chain reaction technique. RESULTS.: The BRAF mutation was absent in tumor DNA samples obtained from patients with benign adenomas, follicular neoplasms or carcinoma, and thyroid lymphoma. In contrast, 5 of 14 PTC tumors were positive for the BRAF mutation. Moreover, 3 of 14 patients with PTC were positive for BRAF mutation in serum and tumor. Of these 3 patients, 2 had lymph node metastasis and 2 had PTC in background of the Hashimoto's thyroiditis. CONCLUSIONS.: The detection of free circulating mutant BRAF in patients with PTC is possible and future studies are warranted to determine its clinical significance.

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Section: Discussionmentioning

confidence: 99%

Detectable BRAF mutation in serum DNA samples from patients with papillary thyroid carcinomas

Chuang

Poeta

et al. 2009

Head & Neck

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“…In Egypt, tissue samples are currently available from only 20–25% of all HCC patients (Ibrahim et al, 2007); however, blood plasma samples are readily available from every patient. Previous studies with breast cancer patients were able to detect promoter methylation in circulating plasma DNA, suggesting a noninvasive approach for early detection of cancer (Papadopoulou et al, 2006). However, the efficacy of conducting DNA methylation studies using plasma DNA from liver cancer patients still has limitations because of the limited sample size or the lack of matching plasma and tumor tissue from the same HCC patient (Chang et al, 2008; Zhang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Concordance of DNA methylation pattern in plasma and tumor DNA of Egyptian hepatocellular carcinoma patients

Iyer

Zekri

Hung

et al. 2010

Experimental and Molecular Pathology

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Hepatocellular carcinoma (HCC) is the fifth most common cancer and the fourth leading cause of cancer mortality globally. HCC incidence has doubled in Egypt in the past 10 years, which could be attributed to the high prevalence of hepatitis C virus (HCV) and hepatitis B virus (HBV), although HBV rates have declined after the introduction of the vaccine in 1992. Aberrant DNA methylation may play an important role in hepatocarcinogenesis. Liver biopsy is the current gold standard for methylation studies; however, imaging techniques often suffice for diagnosis making tissue samples increasingly scarce. The efficacy of conducting DNA methylation studies in molecular epidemiology using plasma DNA is still unclear. We compared tumor methylation profile for the tumor suppressor genes APC, FHIT, p15, p16, and E-cadherin in tumor tissues and plasma to test the concordance between the two types of specimen from the same HCC patients. Twenty-eight HCC patients with matching tissue and plasma DNA were recruited from a case—control study in Gharbiah, Egypt. Concordance between the tissue and plasma was statistically significant in all five genes as follows: APC (23/28, 82.1%, p=0.001), FHIT (24/28, 85.7%, p=.0001), p15 (25/28, 89.2%, p=0.045), p16 (19/28, 67.9%, p=0.037), and E-cadherin (22/28, 78.5%, p=0.0008). The average specificity was 90%, 86%, 96%, 86%, and 100%, respectively. There was no significant association between methylation and hepatitis viral infection for any of the genes tested in this study. Plasma DNA can be reliable for testing methylation profile in liver cancer patients in this population. Future studies on a larger sample size should investigate methylation profile in populations with higher rates of HBV, HCV, and other risk factors.

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“…However, their biological functions may significantly differ. Serum levels of PSMA or its DNA increase as prostate cancer progresses; consequently, it is useful as a clinical marker for diagnosis and prognosis of prostate malignancy (Missiades et al, 2004;Chen et al, 2005;Papadopoulou et al, 2006). FOLH1 hydrolyzes the polyglutamate side chain from folic acid permitting dietary folate absorption into the small intestine.…”

Section: Introductionmentioning

confidence: 99%

Promoter analysis of human glutamate carboxypeptidase II

et al. 2007

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The expression of glutamate carboxypeptidase II (GCP II) is reduced in selective brain regions in schizophrenic patients. To investigate transcriptional mechanisms regulating the human GCP II gene, a 3460 bp DNA fragment comprised of the proximal 3228 bp of 5′ untranscribed sequence and first 232 bp of 5′ UTR portion of this gene was cloned into the mammalian luciferase reporter gene vector pGL3-Basic. Transfection assays in human astrocyte-derived SVG and human prostate tumorderived LNCaP cells demonstrated that constructs with 3460, 1590 and 761 bp portions of 5′ region of human GCP II gene were able to drive the luciferase reporter gene. Additional deletion constructs showed that in the SVG cell line, constructs with 511 and 411 bp of GCP II gene fragments yielded highest transcriptional activity, with declining activity upon further removal of 5′ sequences. Fifteen bp of the promoter 5′ to a 225 bp GCP II fragment were essential for luciferase expression. Thus, in the SVG cells, the proximal 240 bp of the human GCP II promoter (232 bp of the 5′ UTR and 8 bp of 5′ untranscribed sequences) may represent the core promoter. Further, while a LyF-1 site lies within and overlaps a transcription start site in the 15 bp sequence, site-directed mutagenesis shows that LyF-1 is not the transcription iniatiator for the "TATA and CAAT" box lacking GCP II gene in the SVG cells. Finally, pattern differences in GCP II gene promoter expression in SVG and LNCaP cells suggest that sequences beyond 240 bp may be important for tissue-specific GCP II expression.

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Cell‐free DNA and RNA in Plasma as a New Molecular Marker for Prostate and Breast Cancer

Cited by 104 publications

References 14 publications

Detectable BRAF mutation in serum DNA samples from patients with papillary thyroid carcinomas

Detectable BRAF mutation in serum DNA samples from patients with papillary thyroid carcinomas

Concordance of DNA methylation pattern in plasma and tumor DNA of Egyptian hepatocellular carcinoma patients

Promoter analysis of human glutamate carboxypeptidase II

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