Philippe Anker

• University of Geneva

We discuss the early history of the structure of DNA and its involvement in gene structure as well as its mobility in and between cells and between tissues in the form of circulating cell-free DNA (cfDNA). This is followed by a view of the present status of the studies on cfDNA and clinical applications of circulating cell-free tumor DNA (ctDNA). T...

Cell-free DNA (cfDNA) has become widely recognized as a promising candidate biomarker for minimally invasive characterization of various genomic disorders and other clinical scenarios. However, among the obstacles that currently challenge the general progression of the research field, there remains an unmet need for unambiguous universal cfDNA nome...

Circulating cell-free DNA (cfDNA) is one of the fastest growing and most exciting areas in oncology in recent years. Its potential clinical uses cover now each phase of cancer patient management care (predictive information, detection of the minimal residual disease, early detection of resistance, treatment monitoring, recurrence surveillance, and...

Circulating cell-free DNA (cfDNA) is one of the fastest growing and most exciting areas in oncology in recent years. Its potential clinical uses cover now each phase of cancer patient management care (predictive information, detection of the minimal residual disease, early detection of resistance, treatment monitoring, recurrence surveillance, and...

While various clinical applications especially in oncology are now in progress such as diagnosis, prognosis, therapy monitoring, or patient follow-up, the determination of structural characteristics of cell-free circulating DNA (cirDNA) are still being researched. Nevertheless, some specific structures have been identified and cirDNA has been shown...

It is known that cancer progresses by vertical gene transfer, but this paradigm ignores that DNA circulates in higher organisms and that it is biologically active upon its uptake by recipient cells. Here we confirm previous observations on the ability of cell-free DNA to induce in vitro cell transformation and tumorigenesis by treating NIH3T3 recip...

Heat map representing the DNA copy number along all chromosomes. Blue represents regions with deletions and red regions with amplifications. A nearly identical pattern of DNA copy number changes between extracellular (SpDNA SW480) and intracellular (DNA SW480) DNA, compared to a normal reference can be observed. (PDF)

Proposed model of tumor progression mediated by horizontal DNA transfer. The scheme at left summarizes the lateral tumor progression in rats. The SW480 xenograft sheds DNA into circulation which transforms DMH initiated colon cells to form tumors. The figure at the right is the proposed model where a primary tumor regardless of its location and typ...

Histological sections of the site of inoculation of SW480 cells. Viable tumor cells are observed at 24 h (A); at 72 h these are decreasing (B), extensive apoptosis and central necrosis are observed at 7 days (C). At 14 days, no viable cells were found (D). (PDF)

Lack of transformation and DNA transfer in primary cells. A. Primary human-foreskin fibroblasts (BB1) exposed for 45 days to the SW480 supernatant failed to transform and to form tumors in nude mice. Negative control was the wild-type BB1 cell line and positive control, NIH3T3 cultured with the SW480 supernatant (NIH3T3+Sp). B. PCR and RT-PCR of vi...

Experimental design to demonstrate horizontal tumor progression in Wistar rats. Rats were treated with the colon carcinogen 1,2-Dimethylhydrazine (DMH) and subcutaneously (s.c.) injected with human SW480 colon cancer cells. (PDF)

Micro PET-CT using 18F-FDG tumor uptake in rats. A rat receiving only DMH, A shows an irregular mass in the abdominal area with a SUV of 2.2 (at second evaluation). The rat receiving DMH and SW480 cells had abdominal areas of masses with a SUV of 4.1 (at second evaluation), indicating the presence of tumor (B). (PDF)

Introduction: J.B. Lamarck in 1809 was the first to present a theory of evolution. He proposed it was due to the adaptation of species to environmental changes, this adaptation being acquired by the offspring. In 1868, Darwin suggested that cells excrete gemmules, which circulate through the body and reach the gonads where they are transmitted to...

It has been proposed that cell-free nucleic acids in the plasma participate in tumorigenesis and the development of metastases via transfection-like uptake of such nucleic acids by susceptible cells. This putative phenomenon is tentatively referred to as "genometastasis." In the present study, we examined the effects on cultured cells of plasma fro...

The analysis of total plasma DNA and the monitoring of leukemic clone-specific immunoglobulin and/or T-cell receptor gene rearrangements for the evaluation of minimal residual disease (MRD) in the plasma may be useful tools for prognostic purposes or for early detection of subclinical disease recurrence in children with acute lymphoblastic leukemia...

A DNA fraction is spontaneously released from living, but not dead or dying, human, other mammalian, avian, amphibian, plant, and prokaryote cells. The spontaneously released DNA fraction has been shown to be (a) present in both actively dividing and nondividing, differentiated cell populations; (b) labile; (c) associated with DNA-dependent RNA or...

In the late 50s and early 60s of the last century, a theoretical fight was taking place between Western and Russian scientists about the theory explaining the mechanism of evolution. According to neo-Darwinism, evolution was the result of hazard and necessity, that is, mutations arriving by chance favoring the survival of the fittest. For the Russi...

Nude mice were injected with DNA released by T lymphocytes previously exposed to inactivated herpes symplex type 1 or polio viruses. The serum of these mice was tested for its neutralizing activity. Injected nude mice synthesized antiherpetic or antipolio antibodies, depending on the antigen used to sensitize the T lymphocytes. Mice injected with D...

The concept of circulating DNA is derived from the early transformation experiments on bacteria. We describe first experiments done with graft hybrids which could be due to circulating DNA. Work on uptake of foreign DNA by eukaryotic cells is then reported. This work led us to discover the phenomenon of transcession in plants and animals where we s...

The human organism is continuously in close contact with microorganisms, especially bacteria. In the present work, by means of a real-time polymerase chain reaction (PCR) technique, we looked for the presence of a distinct bacterial gene in human cells. To this end, we cultured a human cell line, HL60, in a supernatant in which bacteria (Bacillus s...

The majority of lung cancer patients have tumor-derived genetic alterations in circulating plasma DNA that could be exploited as a diagnostic tool. We used fluorescent microsatellite analysis to detect alterations in plasma and tumor DNA in 34 patients who underwent bronchoscopy for lung cancer, including 11 small cell lung cancer (SCLC) and 23 non...

BACKGROUND: In addition to cell lysis, apoptosis has been advanced as the origin of circulating DNA on the basis of several observations. Plasma or serum DNA often presents a ladder pattern reminiscent of that displayed by apoptotic cells when subjected to electrophoresis. However, the phenomenon of active release of DNA from cells might also be ex...

BACKGROUND: Nucleic acids can be found in small amounts in healthy and diseased human plasma/serum. Higher concentrations of DNA are present in the plasma of cancer patients sharing some characteristics with DNA of tumor cells. Together with decreased strand stability, the presence of specific oncogene or tumor-suppressor gene mutations, microsatel...

Small amounts of DNA circulate freely in plasma or serum, but the mechanism of release is not known. To determine if DNA is actively excreted from viable cells, we utilized real-time PCR to measure the proportion of Alu repeat sequences compared to the β-globin gene in serum and lymphocyte DNA in 27 cancer patients and 22 healthy controls. The prop...

Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.

Tumor-derived circulating DNA has been found in the plasma of cancer patients. Alterations include decreased strand stability, mutations of oncogenes or of tumor suppressor genes, microsatellite alterations, and hypermethylation of several genes. RNA has also been found circulating in the plasma of normal subjects and cancer patients. Tyrosinase mR...

Small-cell lung cancer (SCLC), one of the major types of lung cancer, is associated with many different somatic molecular genetic changes. These alterations, observed in tumor DNA, have also been identified in the plasma DNA of patients. We undertook the present study to make a prospective investigation into the correlation between abnormal plasma...

Although it is evident that DNA circulates freely in blood plasma both in disease and in health, the source of this DNA remains enigmatic. It can be presumed that circulating DNA in healthy subjects derives from lymphocytes or other nucleated cells. Yet, it is not known why cancer patients have such large quantities of plasma DNA. There is no doubt...

Small amounts of DNA circulate in both healthy and diseased human plasma/serum, and increased concentrations of DNA are present in the plasma of cancer patients. Characteristics of tumor DNA have been found in genetic material extracted from the plasma of cancer patients. These features include decreased strand stability, the presence of specific o...

Chromosomal abnormalities are associated with the development of breast cancer, and widespread allelic loss or imbalance is frequently found in tumor tissues taken from patients with this disease. Using different markers, we studied a total of 61 patients (divided into three groups) for the presence of microsatellite instability and loss of heteroz...

Small amounts of free DNA circulate in both healthy and diseased human plasma/serum, and increased concentrations of DNA are present in the plasma of cancer patients. Characteristics of tumour DNA have been found in genetic material extracted from the plasma of cancer patients. These features include decreased strand stability and the presence of s...

Human tumors exhibit two fundamentally important characteristics, extensive genetic alteration and clonality. Although it is still unclear to what extent tumors have an elevated mutational burden as compared with normal tissue, their clonality results in their ready detection. Thus, assaying tissues for clonal alterations at frequently mutated micr...

Deletions of DNA sequences on chromosome 3p [loss of heterozygosity (LOH)] are characteristic of clear cell renal carcinoma, which accounts for about 80% of all renal malignancies. Comparing tumor DNA to DNA from normal cells, LOH analysis of microsatellite sequences has aided in molecular diagnosis of renal carcinoma. Because clinically useful tum...

K-ras mutations are frequently found in primary pancreatic adenocarcinomas. In this prospective study, we looked for K-ras mutations in the plasma of patients with pancreatic cancer. We isolated plasma DNA from 21 pancreatic cancer patients using a simple and rapid extraction technique and detected K-ras alterations with a PCR assay and subsequent...

Circulating DNA can be isolated from the plasma of healthy subjects and from patients with cancer. The aim of this study was to detect K-ras mutations in DNA extracted from the plasma of patients with colorectal cancer. Tumor and plasma DNA were extracted from 14 patients with colorectal cancer (stages A-D), and K-ras alterations were detected usin...

Microsatellite instability is an important characteristic of many tumor types especially those associated with hereditary non-polyposis colorectal carcinoma (HNPCC) syndrome. Microsatellite alterations in 50% of primary small cell lung carcinoma (SCLC) have been found. These alterations were also found in the sputum. Because neoplastic characterist...

Microsatellite DNA alterations are an integral part of neoplastic progression and are valuable as clonal markers for the detection of human cancers. Moreover, recent evidence suggests that senescent tumor cells may release DNA into the circulation, which is subsequently carried by and therefore enriched in the serum and plasma. We tested 21 patient...

K-ras point mutations in the blood plasma DNA of patients with colorectal tumors.

Anc. Comptes Rendus de L'Academie des Sciences. Serie III, Sciences de la vie [1994, 317(10):869-874] The spontaneous release of a glyconucleoprotein complex in the supernatant of eukaryote cell cultures is a general phenomenon independent of cell lysis. The DNA recovered from this glyconucleoprotein material contains most part of the genome. The...

Oncogene mutations are frequently found in several tumour types and, among these, point mutations of the ras gene are particularly significant. A predominance of N-ras mutations has been found in the bone marrow DNA of patients with myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML). On the other hand, increased levels of plasma DN...

Oncogene mutations are frequently found in several tumour types and, among these, point mutations of the ras gene are particularly significant. A predominance of N-ras mutations has been found in the bone marrow DNA of patients with myelodysplatic syndrome (MDS) or acute myelogenous leukaemia (AML). On the other hand, increased levels of plasma DNA...

About one third of patients with various malignant diseases were found to have extractable amounts of DNA in their plasma whereas no DNA could be detected in normal controls. Using the test established by one of us (M.B.), which is based on decreased strand stability of cancer cell DNA, we have found that several plasma DNA originate from cancer ce...

Unlabelled: Ten out of 37 patients with advanced malignant diseases were found to have extractable amounts of DNA in their plasma whereas no DNA could be detected in 50 normal controls. After its purification from the original nucleoprotein complex, DNA plasma levels ranging from 0.15 to 12 micrograms/ml were measured, the lowest concentration det...

Nude mice were injected with DNA purified from the nucleoprotein complex released by T lymphocytes previously exposed in vitro to inactivated herpes or poliovirus. After five days the serum of these mice was tested for its virus neutralizing activity. Results show that injected nude mice synthesize antiherpetic or antipolio antibodies depending on...

Nude mice were injected with DNA released by human T lymphocytes previously exposed to inactivated herpes virus. After 4 days a virus neutralization test showed that the serum of some mice contained antiherpetic antibodies. These antibodies carried human allotypes.

Human lymphocytes obtained from donors exhibiting different allotypes were separated into B- and T-enriched subpopulations and cultured in the presence or absence of Herpes simplex virus inactivated by U.V. Isolated B or T cell suspensions did not produce any antiherpetic activity. The B lymphocytes cultured in the presence of the supernatant colle...

Human lymphocytes obtained from donors exhibiting different allotypes were separated into B and T subpopulations and cultured in presence or in absence of UV-inactivated Herpes simplex virus. Isolated B or T cells did not produce antiherpetic activity. The B lymphocytes, cultured in presence of the supernatant collected from virus exposed T cells o...

Lymphocytes carrying different allotypes were separated into B and T subpopulations and cultured in presence or in absence of U.V. inactivated Herpes simplex virus. The B lymphocytes cultured in presence of 1% of the supernatant collected from virus exposed T cells, synthesized an anti-herpetic antibody with some allotypic markers of the T cell don...

Both antigen-stimulated and non-stimulated human blood lymphocytes release in vitro a DNA-containing complex which is not the product of dying or disintegrating cells. Lymphocytes obtained from different PPD or HBs positive or negative donors were incubated with one of these antigens and the DNA released in the culture medium was tested for its inf...

Human blood lymphocytes carrying different allotypes were divided into B and T subpopulations and cultured in presence or in absence of ultraviolet inactivated Herpes Simplex Virus. Isolated B or T cells did not produce any antiherpetic activity. The B lymphocytes cultured in presence of 1 or 50% of the supernatant collected from virus exposed T ce...

Cell systems as different as normal human blood lymphocytes and frog auricles release spontaneously a nucleoprotein complex in their culture medium. This release seems to be an active mechanism that is unrelated to cell death. The presence of RNA in this complex is demonstrated. The amount of extracellular RNA is regulated by the same homeostatic m...

Unstimulated human blood lymphocytes have been shown to release in vitro a complex containing DNA and RNA. These nucleic acids are composed of newly synthesized material and appear to be released according to a homeostatic mechanism. Extracellular synthesis of the released DNA has been demonstrated by using a nearest neighbor analysis technique. Th...

Publisher Summary This chapter discusses the circulating nucleic acids in higher organisms. DNA is able to leave bacteria and enter other bacteria and the mechanisms and situations involved are readily understood. Bacterial DNA can move from members of one strain to those of another by means of conjugation or transduction, which does not strictly i...

Human lymphocytes were shown to release, in vitro and in the absence of any stimulation, a complex containing DNA. It has also been reported that the release process is unrelated to cell death and is regulated by a homeostatic mechanism. Some properties of the extracellular DNA were investigated. When a phosphorylated precursor was added to the cel...

Human blood lymphocytes released DNA in vitro in the absence of any stimulation. Once purified from the complex appearing in the supernatant, this DNA exhibited typical characteristics as shown by its UV absorption curve, its deoxyribose coloration, and its sensitivity to DNase. Elution patterns on hydroxyapatite columns indicated that the excreted...

Exogenous DNA has been administered to roots of Vicia faba in which this DNA stimulates an increase in acid deoxyribonuclease activity. This enzyme activity is associated with vesicles which follow whatappears to be the cytological pathway of foreign DNA in host tissues.

H-DNA from Escherichia coli has been fed to cut shoots of Lycopersicon esculentum. Autoradiographic studies have shown the bacterial DNA to be localized in the nuclei, plastids, and mitochondria of cells in the phloem, cambium, parenchyma, collenchyma, and epidermis. Two populations of cells were detectable, namely, those with nuclei in which the ³...

After frog auricles have been in contact with a suspension of bacteria or bacteria-free supernatant fluid, newly synthesized bacterial ribonucleic acid (RNA) is recovered in animal cells. It appears that the presence of bacterial deoxyribonucleic acid (DNA)-dependent RNA polymerase is necessary for the transcription of bacterial DNA in the host cel...

Frogs were injected intraperitoneally with bacteria, and the RNA of the brains (which have protective barriers against the bacteria used) was extracted. Part of the RNA was bacterial RNA apparently resulting from the transcription of DNA transferred from bacteria to the brain cells.

Des organes de plantes ou d'animaux mis dans une suspension bactrienne synthtisent du RNA bactrien. Ce phnomne que nous avons appel transcession est d au transfert de DNA spontanment cd par les bactries vivantes aux cellules des organismes suprieurs. Dans le prsent travail, il est dmontr que le mme phnomne peut avoir lieu naturellement lorsqu'une g...

DNA has been found in the culture medium of bacteria and of isolated frog auricles. The small quantity of lysed bacteria or dead cells cannot account for the high amount of DNA released. The released DNA is sensitive to DNase but is less degraded than the DNA isolated from the cells. The deoxyribose of the released DNA can be revealed by indole but...

We have chosen internodes of spinach stems because they have insignificant mitotic activity in our experimental conditions (divisions are very rare in the differentiated tissues2). The stem has a high metabolic activity as the cells grow to a very large size while keeping their photosynthetic activity.

Purified Agrobacterium tumefaciens deoxyribonucleic acid (DNA) does not produce crown gall tumors in growing plants, conditioned by wounding, as the living bacteria do. Purified bacterial DNA migrates in the plant and replicates, but it is not transcribed in our experimental conditions. On the contrary, when DNA is released naturally from bacteria...

After plants have been in contact with a suspension of bacteria one finds in plant cells self replicating bacterial DNA and replicating molecules formed of bacterial DNA combined with plant DNA. Moreover newly synthesized bacterial RNA appears in the host cell. These phenomena seem to be due to a transfer of bacterial DNA into plant cells.

BACTERIAL RNA has been recovered from the cells of shoots dipped in a suspension of Agrobacterium tumefaciens (strain B6), virulent to plants1. We have now found that this is a general phenomenon, resulting from the release of nucleic acids into plant cells.

Thèse : Sc. Biologiques : Genève : 1969 ; 1492.

Résumé L'effet du citrate de sodium sur la translation d'ADN d'origine bactérienne chez la tomate a été étudié biochimiquement et par autoradiographie. Les plantes prétraitées au citrate prennent plus d'ADN étranger que les plantes témoins. En revanche le citrate n'a pas d'effet sur la dépolymérisation du DNA pris par la plante. Les relations entre...

FOREIGN DNA can enter the cell nuclei of tomato plants, but its composition remains largely unaltered1-3. When tritiated bacterial DNA is taken up by tomato plants, all the DNA can be isolated and centrifuged on a caesium chloride gradient. The radioactive molecules are of two kinds: one having the density of the tomato DNA, the other that of the f...

Résumé Nous avons étudié l'influence de différentes températures sur la translation de l'ADN d'origine bactérienne chez les plantules de tomate. La température n'a aucune influence en elle-même. Néanmoins des variations de température diminuent la dépolymérisation de l'ADN étranger migré dans la plante.

STUDIES of the incorporation of labelled thymidine into the DNA of heart muscle and skeletal muscle in adult animals have shown significant values which indicate regular renewal of some or all of the DNA in these non-dividing organs1,2. Autoradiography has shown labelled muscle nuclei in smooth muscle and in heart muscle and therefore subsidiary ce...

Résumé Nous avons étudié l'influence de la lumière sur la translation de l'ADN d'origine bactérienne chez des plantules de tomate. La lumière augmente la prise d'ADN étranger. Cet ADN est, par contre, dans un état moins polymérisé que chez les plantules exposées à l'obscurité. Dans les mêmes conditions expérimentales, la lumière n'a aucune influenc...

WE have previously reported1,2 results showing that exogenous tritiated DNA molecules can migrate in the xylem of tomato plant and, after some degradation, be taken up by the meristematic cells. We now report our investigation of the nature of the radioactive molecules recovered after incubation of the plant by bacterial DNA using ultracentrifugati...

IT has been shown that exogenous tritiated DNA can be taken up by germinating barley seeds and be transferred from the endosperm to the growing roots without much degradation, while in the shoots it is apparently destroyed1,2.