Identification of Loss of Heterozygosity on Circulating Free DNA in Peripheral Blood of Prostate Cancer Patients: Potential and Technical Improvements

Müller, Imke; Beeger, Cord; Alix‐Panabières, Catherine; Rébillard, Xavier; Pantel, Klaus; Schwarzenbach, Heidi

doi:10.1373/clinchem.2007.099333

Cited by 39 publications

(40 citation statements)

References 33 publications

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“…To determine the lowest portion of tumor-specific DNA that can be flawlessly detected, dilution experiments were done. For this study, we mixed and amplified known quantities and proportions of normal (PBMC) DNA and plasma DNA, as described before (25).…”

Section: Methodsmentioning

confidence: 99%

Cell-free Tumor DNA in Blood Plasma As a Marker for Circulating Tumor Cells in Prostate Cancer

Schwarzenbach

Alix‐Panabières

Müller

et al. 2009

Clinical Cancer Research

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220

141

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Purpose: Circulating cell-free DNA in the blood of cancer patients harbors tumor-specific aberrations. Here, we investigated whether this DNA might also reflect the presence of circulating tumor cells (CTC). Experimental Design: To identify the source of cell-free DNA in blood, plasma derived from 81 patients with prostate cancer was examined for CTCs and cell-free DNA. An epithelial immunospot assay was applied for detection of CTCs, and a PCR-based fluorescence microsatellite analysis with a panel of 14 polymorphic markers was used for detection of allelic imbalances (AI). Results: The plasma DNA levels significantly correlated with the diagnosis subgroups of localized (stage M0, n = 69) and metastasized prostate cancer (stage M1, n = 12; P = 0.03) and with the tumor stage of these patients (P < 0.005). AI was found on cell-free DNA in plasma from 45.0% and 58.5% of M0 and M1 patients, respectively. Detection of CTCs showed that 71.0% or 92.0% of the M0 and M1 patients harbored 1 to 40 CTCs in their blood, respectively.The occurrence of CTCs correlated with tumor stage (P < 0.03) and increasing Gleason scores (P = 0.04). Notably, significant associations of the number of CTCs with the AI frequencies at the markers D8S137 (P = 0.03), D9S171 (P = 0.04), and D17S855 (P = 0.02) encoding the cytoskeletal protein dematin, the inhibitor of the cyclin-dependent kinase CDKN2/p16 and BRCA1, respectively, were observed. Conclusions: These findings show, for the first time, a relationship between the occurrence of CTCs and circulating tumor-associated DNA in blood, which, therefore, might become a valuable new source for monitoring metastatic progression in cancer patients.

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Section: Methodsmentioning

confidence: 99%

Cell-free Tumor DNA in Blood Plasma As a Marker for Circulating Tumor Cells in Prostate Cancer

Schwarzenbach

Alix‐Panabières

Müller

et al. 2009

Clinical Cancer Research

Self Cite

220

141

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“…На сегодняшний день много работ посвящено изучению микросателлитных перестроек в цирДНК крови [107][108][109][110][111][112][113]. Микросателлиты -короткие повторяющиеся и высокополиморфные последовательности, состоящие из многократно повторяющегося мотива, например, ди-, три-, тетрануклеотида: (NN-N)n. Микросателлиты более или менее случайно распределены в геноме [114].…”

Section: особенности строения внеклеточных днк кровиunclassified

“…Биологическая функция микросателлитов неясна, однако они часто используются в качестве генетических маркеров для анализа расположения генов-супрессоров опухолей и т.д. Опухолеассоциированные нарушения микросателлитной ДНК были обнаружены в цирДНК плазмы крови при раке лёгких [107], головы и шеи [108], почки [109], мочевого пузыря [110], предстательной железы [111,112] и гепатоцеллюлярной карциноме [113].…”

Section: особенности строения внеклеточных днк кровиunclassified

“…Достоверная корреляция между потерей гетерозиготности в цирДНК плазмы крови, анализируемой при помощи ПЦР, и увеличением показателя Глисона была обнаружена у больных раком предстательной железы [111] при комбинации маркеров D6S1631*D8S286*D9S171 и D8S286*D9S171.…”

Section: особенности строения внеклеточных днк кровиunclassified

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Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

Bryzgunova

Laktionov

2015

BIOMED KHIM

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Внеклеточные нуклеиновые кислоты (внНК) в циркуляции как здоровых, так и больных людей были впервые описаны в 1948 г., однако оставались без внимания до середины 60-х годов прошлого века. внНК особенно интенсивно исследуются в последние 5 лет. Основное внимание уделяется исследованию внНК как источнику диагностического материала; однако механизмы генерации внеклеточных нуклеиновых кислот, а также механизмы, обеспечивающие их долговременную циркуляцию в кровотоке, однозначно не установлены. По данным одних авторов, основным источником циркулирующих дезоксирибонуклеиновых кислот в крови (цирДНК) являются процессы некроза и апоптоза, другие ссылаются на возможную секрецию нуклеиновых кислот как здоровыми, так и опухолевыми клетками. Известно, что цирДНК могут циркулировать в крови в течение длительного времени, ускользая от действия ДНК-гидролизующих ферментов крови и, по-видимому, находясь в составе надмолекулярных комплексов. В этом обзоре представлены данные разных авторов и приведены доказательства в пользу всех предложенных теорий появления цирДНК, описаны особенности строения цирДНК, а также факторы, влияющие на время циркуляции ДНК в крови.Ключевые слова: циркулирующая ДНК, апоптоз, некроз, активная секреция, ДНКазы, метилирование.

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“…Detection of LOH in cell-free circulating DNA may be constrained by the restrictions mentioned above. Muller et al [93] have attempted to overcome this dilemma by taking advantage of a PCR-based fluorescence microsatellite assay for 12 polymorphic markers for the purpose of investigating LOH in the cell-free plasma DNA of 59 prostate cancer patients. To enrich the DNA portion containing shorter fragments [94], fractionation of plasma DNA into high and low molecular weights was performed.…”

Section: Corrections Of Technical Bias In the Cell-free Circulating Nmentioning

confidence: 99%

Circulating DNA as a Biomarker for Early Detection of Cancer: A Brief Update with an Emphasis on Lung Cancer~!2010-06-09~!2010-08-03~!2010-09-06~!

Cabral¹

2010

TOLCJ

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Abstract:In most cases, early detection and treatment of cancer are prerequisites for full recovery. However, its early detection continues to be extremely difficult since its characteristic symptoms rarely manifest at the onset of disease. The development of highly sensitive, specific biomarkers also capable of reflecting pathological changes is, therefore, of the upmost importance. Lung cancer, for example, is most frequently diagnosed during the late metastatic stage so that, as a result, malignant neoplasms in the lung are among the leading causes of cancer-related deaths worldwide. Circulating DNA is a non-invasive diagnostic assay that has been greatly improved for the purposes of diagnosis, prognosis, and treatment of cancer. In the current review, we discuss recent data concerning circulating tumor-derived DNA as a tool for early detection, diagnosis, and follow-up. Given the scope of this review, the focus will be on lung cancer, one of the most prolific and lethal cancers affecting humanity today.

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Identification of Loss of Heterozygosity on Circulating Free DNA in Peripheral Blood of Prostate Cancer Patients: Potential and Technical Improvements

Cited by 39 publications

References 33 publications

Cell-free Tumor DNA in Blood Plasma As a Marker for Circulating Tumor Cells in Prostate Cancer

Cell-free Tumor DNA in Blood Plasma As a Marker for Circulating Tumor Cells in Prostate Cancer

Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

Circulating DNA as a Biomarker for Early Detection of Cancer: A Brief Update with an Emphasis on Lung Cancer~!2010-06-09~!2010-08-03~!2010-09-06~!

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