Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Antineoplastic Agents

All Drugs and Chemicals

Azacitidine

The investigators will analyze the genomic features of clonal dominance and ineffective hematopoiesis in elderly subjects enrolled in two population-based studies: "Health and Anemia" study \[Haematologica 2010;95:1849\], and "Monzino 80-plus" study \[BMC Neurol.2011;11:54, validation cohort\]. Overall in 5000 subjects aged \>65y peripheral blood samples (in some cases collected at different time points) will be available for biological investigations.

The investigators will base on large retrospectove adult MDS population with comprehensive genomic and clinical data available within EuroBloodNet network (data on 3000 patients will be available), to accurately predict clinical outcomes in MDS at individual-patient level.

The investigators plan to define 2 homogenous clinical cohorts (learning and testing cohort at 2:1 ratio) in order to define distinct patterns and genetic groups within MDS and to independently validate their predictive value.

The investigators will analyze MDS patients enrolled in prospective clinical trials conducted within the EuroBloodNet network. Overall 350 patients treated with azacitidine from prospective studies (VidazaAllotrial, RELAZA02 trial, AZA-Ida study, intensive AZA study) will be available for biological investigations to define biomarkers associated with clinical response. Validation of biomarkers will then be performed in an independent cohort including 320 patients (AZA-PLUS trial). In all these studies, biobanking of bone marrow (BM) and peripheral blood (PB) samples has been systematically performed, providing a unique resource to be investigated within this proposal.

Matteo Della Porta, MD

Maria Elena Bicchieri, PhD

Pierre Fenaux, MD

Uwe Platzbecker, MD

Francesc Sole, MD

Rationale Myelodysplastic syndromes (MDS) are rare cancers with unmet medical needs. Study of MDS has been rapidly transformed by genome characterization.

The investigators hypothesize that comprehensive analyses of large patient population will allow to correctly estimate the effect of each mutation on clinical outcomes, and that niche factors and immune dysfunctions may influence the development of MDS, clonal evolution and response to treatments

Aims

1- Investigate gene mutations, niche factors and immune dysfunctions influencing the development of MDS, and define biomarkers for early identification of individuals at risk; 2- Develop prognostic models for MDS patients through integration of comprehensive genomic/clinical information; 3- Define biomarkers to better stratify the individual probability of response to specific treatments

Methods EuroBloodNet, the European Reference Network in rare hematological diseases, will provide a basis for research activities. Study of genomic features of clonal dominance in elderly subjects enrolled in large population-based studies and description of the dynamics of clonal establishment and evolution; study of bone marrow microenvironment to identify immune dysfunctions influencing MDS development. Development of inclusive statistical models to accurately predict clinical outcome at individual level, based on large MDS populations with comprehensive genomic/clinical data. Finally, analysis of mutational screening and immune profiles from patients enrolled in prospective trials, to provide evidence on genetic/immunologic profiles associated with probability of response to specific compounds

Expected results To characterize how clonal hematopoiesis relates to the induction of MDS clinical phenotype, and to test the utility of gene sequencing to detect subjects at risk of developing MDS. To define effective prognostic systems and biomarkers to stratify the individual probability of response to treatment

MDS typically occurs in elderly people and a portion of these subjects evolve into acute myeloid leukemia (AML). The natural history of MDS is highly heterogeneous, and therefore a risk-adapted treatment strategy is mandatory.

The presence of mutations in a given individual has only limited predictive power, as conversion to MDS is rare regardless of mutation status. In addition, in patients with overt MDS, genetic abnormalities explain only a proportion of the total hazard for survival, meaning that a large percentage is still associated with clinical and non-mutational factors. Comprehensive analyses of large patient populations are warranted to correctly estimate the independent effect of each mutation on clinical outcome and response to treatment.

Moreover, environmental factors influencing the development of MDS and the probability of response to specific treatments are to be characterized. They include alterations in the immune system. In this context, a significant association was found between autoimmune disorders and MDS, and activation of the inflammasome may contribute to MDS development

AIMS 1- Investigate gene mutations, niche factors and immune dysfunctions influencing the development of MDS, and define biomarkers for early identification of individuals at risk; 2- Develop prognostic models for MDS patients through integration of comprehensive genomic/clinical information; 3- Define biomarkers to better stratify the individual probability of response to specific treatments

EXPERIMENTAL DESIGN

AIM1

1a) The investigators will analyze the genomic features of clonal dominance and ineffective hematopoiesis in elderly subjects enrolled in different population-based studies.

Peripheral blood samples will be available for biological investigations. A low-cost, high-throughput platform for mutation screening of 72 genes known to be relevant in MDS will be used.

1b) In order to gain further insight into the MDS genetic heterogeneity, the investigators will perform DNA sequencing in hematopoietic progenitors single cells to clarify the clonal architecture of marrow dysplasia in HSC, the dynamics of clonal establishment and expansion during hematopoietic differentiation, and their relationship with the disease phenotype and evolution

1c) In selected elderly individuals, the investigators will study the transcriptome (RNA sequencing) of isolated mesenchymal stromal cells (MSC) and marrow microenvironment (i.e., innate ad adaptive immunity) with the aim to identify niche factors that may influence the development of a MDS phenotype in elderly subjects with clonal hematopoiesis. Moreover, in patients suffering from both MDS and autoimmune disorder, the investigators will analyze immunological parameters. They will be compared with those of patients with MDS but without immune disorder, and patients with immune disorders without MDS

AIM2

In myeloid malignancies, it was shown that large knowledge banks of matched genomic-clinical data can improve clinical decision-making.

In the present project, basing on large MDS populations with comprehensive genomic and clinical data available within EuroBloodNet network (data on \>3000 patients will be available), the investigators will develop inclusive, multistage statistical models (Bayesian network analysis and clustering) to accurately predict clinical outcomes in MDS at individual-patient level. The investigators plan to define 2 homogenous clinical cohorts in order to define distinct patterns and genetic groups within MDS and to independently validate their predictive value. As a research tool, the investigators plan to create a prototype portal within our EuroBloodNet website that allows outcome predictions to be generated based on this data set for user-defined constellations of genomic features and clinical variables. The reliability of this tool on clinical decision making will be tested in a prospective observational trial in the context of EuroBloodNet

AIM3

The investigators will analyze the mutational status and immune landscape associated with response to HMA in MDS patients enrolled in prospective clinical trials conducted within the EuroBloodNet network. Patients treated with azacitidine from prospective studies will be available for biological investigations to define biomarkers associated with clinical response. Validation of biomarkers will then be performed in an independent cohort. In all these studies, biobanking of bone marrow (BM) and peripheral blood (PB) samples has been systematically performed, providing a unique resource to be investigated within this proposal. Data on mutational screening and immune profiles are already available in most patients, and were obtained by comparable methods. For mutation screening, a NGS approach covering key genes involved in myeloid malignancies and the response to HMA was used. For a comprehensive immunological characterization of T lymphocytes, NK cells and ILC cells, standardized flow cytometric protocols were used, which will provide novel insights into frequency, differentiation and activity of these cells in response to therapy. Complementary immunoassays based on Luminex technology will be used to quantify secretory proteins (cytokines, chemokines, growth factors) in BM and PB plasma samples.

An European Platform for Translational Research in Myelodysplastic Syndromes

An Integrated European Platform to Conduct Translational Studies in Myelodysplastic Syndromes Based on the EuroBloodNet Infrastructure

The investigotors will study the prevalence and type of somatic mutations by a low-cost, high-throughput platform including 72 genes, relevant in myeloid neoplasms.

The investigators will study the genes diffentially expressed between cell populations of interest and normal controls

The investigators will define, by innovative bayesian and clustering models, independent clinical and molecular factors associated to the probability of survival and response to specific treatments.

The investigators will analyse by flow-cytometry the frequency of T lymphocytes, NK cells and ILC cells during different disease stages and in response to therapy.

Complementary immunoassays based on Luminex technology will be used to quantify secretory proteins (cytokines, chemokines, growth factors).

Istituto Clinico Humanitas

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Breast Neoplasms

Neoplastic Cells, Circulating

Breast Diseases

Skin Diseases

Miguel Martín, Ph

Characterization of the driver mutations in an individual metastatic breast cancer patient is critical for many reasons. Effective targeted therapies require identifying genomic alterations in the tumoral tissue. The scarce efficacy of many currently available targeted drugs may be due to the outbreak of resistant clones with different genotype that already present at the initiation of therapy. It is well known the intra-tumor heterogeneity with genetic and non-genetic factors considered as the origin of the tumor cell-clon composition. The acquisition of multiple mutations (driver and passenger), altogether with the stage of differentiation, according to the cancer stem cell hypothesis, confers to the tumor cells clinically important properties, such as resistance to therapies and seeding abilities.

Moreover, there is a current challenge in establishing whether the metastatic cells arise from the most aggressive and dominant clone in the primary tumor or the metastasic tissue diverges with substantial genetic changes very early in the evolution of the disease. Primary and metastatic tumor may have a close clonal relationship or evolve in parallel and acquire different genomic alterations. In the real life, it is plausible that both models coexist with different predominance according to the tumoral tissue and etiology.

The study hypothesizes that breast cancer metastases and primary tumors could harbor different genomic profiles related to genomic regions of interest in a clinically relevant proportion of metastatic breast cancer patients.

Moreover, the genomic aberrations found in the metastatic breast cancer tissue could also be detected in CTCs and circulating free DNA.

If true, CTCs and circulating free DNA would be convenient, non-invasive, easily accessible sources of genomic material for the analysis of mutations and other genomic aberrations.

Primary and Metastatic tumoral tissue (FFPE samples) and Blood samples

Characterization & Comparison of Drugable Mutations in Primary and Metastatic Tumors, CTCs and cfDNA in MBCpatients

Characterization and Comparison of Drugable Mutations in Primary Tumors, Metastatic Tissue, Circulating Tumor Cells and Cell-Free Circulating DNA in Metastatic Breast Cancer Patients

Note: circulating tumor cells couldn't be sequenced

Hospital General Universitario Gregorio Marañon

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Nervous System Diseases

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Carcinoma

Carcinoma, Renal Cell

Von Hippel-Lindau Disease

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neurocutaneous Syndromes

Angiomatosis

Vascular Diseases

Ciliopathies

Congenital Abnormalities

Abnormalities, Multiple

Genetic Diseases, Inborn

Healthy volunteers; patients referring to San Raffaele Hospital for renal/urological conditions other than VHL

Individuals with genetic diagnosis of Von Hippel Lindau disease

One whole blood sample per individual (3 ml) will be collected. Up to 5 urine samples per individual will be collected

Blood and urine sample collection

Irene Franco, PhD

Daniela Canibus, BsC

Daniela Canibus, Bsc

Alessandro Larcher, MD

Andrea Salonia, MD

The goal of this observational study is to analyze somatic mutations in the genome of normal kidney cells from patients affected by kidney cancer predisposition syndrome Von Hippel Lindau (VHL) and compare the mutation rates observed in these patients and in individuals not affected by the disease. The main questions the study aims to answer are:

* Do kidney cells from VHL patients mutate more than cells from control individuals during adult life?
* What mechanisms favor somatic mutation occurrence in the genome of normal kidney tubule cells?

Participants will donate one blood sample and multiple urine samples. Urines will be used for kidney cell isolation, followed by cell culturing and genetic analyses. Urine samples will be collected once a year for 3-5 years. Sample collection will occur during the yearly screening program that each patient undergoes at the hospital. In case patients undergo surgical treatment of kidney tumors, samples discarded from surgery (tumor and normal kidney adjacent to tumor) will be collected and subjected to genetic analyses.

Researchers will compare the number and types of mutations found in tumors and normal kidney cells from VHL-disease patients with those found in normal kidney cells from control individuals, to see if somatic mutation rates are increased in VHL-disease patients during aging.

whole blood, urine samples, kidney tumor biopsies, kidney cyst biopsies, normal kidney tissue adjacent to tumor biopsies

Mechanisms of Somatic Mutation and Tumor Initiation in Pre-malignant Kidney Tubule Cells

The genome of multiple normal kidney cells from each subject will be investigated by whole genome sequencing. The number of somatic mutations per genome will be plotted according to donor's age and a curve describing the accumulation of mutations with age will be obtained for both the control and VHL-disease patient populations. The aim is to assess differences in mutation rates in the kidney of VHL-disease patients vs controls and understand the underlying mechanism.

From each urine sample, researchers can culture up to 20 single cell clones and perform a single-clone, gene-expression analysis. The expression of markers that characterize the mutation-prone, pre-cancer population will be assessed in all clones. The fraction of clones expressing markers of pre-cancer cells will be calculated in control and VHL-disease groups. The aim is to assess any differences in the presence of pre-cancer cells in urines from VHL-disease patients vs controls and assess any correlation of this parameter with kidney cancer occurrence.

Università Vita-Salute San Raffaele

IRCCS San Raffaele

Doctor

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Genital Diseases, Female

Genital Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Participants must have suspected or confirmed upper genital tract cancer (uterine, tubal and ovarian) and must be scheduled to undergo surgery for tumor removal.

Patients will undergo uterine sampling with DOvEEgene Fleur endometrial sampling device prior to surgical intervention, in addition to standard of care treatment.

DOvEEgene Fleur Sampling

Dr. Lucy Gilbert, MD,MSc,FRCOG

Dr. Claudia Martins, PhD

This study is related to a previous study from the same group which started in 2014 (NTC02288676, McGill REB A08-M79-13B, MUHC REB 2020-5945) to develop a clinically implementable screening test -DovEEgene: developing and validating a novel molecular test for the early diagnosis of cancer of the endometrium, tubes and ovaries. This study is designed to identify endometrial, tubal and ovarian cancer very early based on identifying cancer-specific mutations (cancer DNA) in a pap sample taken from inside the uterus. The results are particularly encouraging given that control group is challenging with high background mutational burden from benign tumours, endometriosis, germ-line mutations etc.

To date, all the intrauterine samples were obtained using the commercially available TAO brush™ which is designed to take an endometrial sample. However, when patient tolerability was assessed using a numerical pain scale (NPS) ranging from 0 (no pain) to 10 (severe pain), patients rated the sampling using the TAO brush™ at 3.5 versus 0 for a cervical pap sample. These results were not surprising as the TAO brush™ was designed for dislodging strips of endometrial tissue to use for histopathologic examination. With respect to the investigators objective, which is to collect cancer cells that have exfoliated to the uterus, a sampler that collects these exfoliated cells with as little disturbance as possible to the underlying endometrium is preferred. In this sub-study, the investigators aim to evaluate a new endometrial sampling tool, the DOvEEgene Fleur, which is believe to be superior to the current TAO brush™ in terms of cancer detection, ease of use and patient tolerability. The sampler has been designed using materials/components found in the TAO brush™ and other approved medical devices.

DOvEEgene Fleur: New Uterine Sampling Tool

Evaluate pain tolerability and acceptability during and after endometrial sample collection. This will be assessed using pain scores reported by participants on numeric pain scale (NPS) ranging from 0 to 10. Final pain scores with the DOvEEgene Fleur will be compared to historical pain scores collected with the TAO brush (Cook Medical).

Ease of use of the DOvEEgene Fleur will be evaluated through a physician feedback form.

Molecular assessment to verify DOvEEgene Fleur is capable of detecting cancer cells from the uterus.

McGill University Health Centre/Research Institute of the McGill University Health Centre

GSE Biomedical

McGill University

Professor Department of Obstetrics & Gynecology and Department of Oncology

Mouth and Tooth Diseases

Carcinoma, Squamous Cell

Mouth Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Oral Squamous Cell Carcinoma

Oral Cancer

Lip and Oral Cavity Cancer

Anti-Infective Agents

Central Nervous System Depressants

Ethanol

A clinical-biological cohort of 30 patients with epidermoid carcinomas of the oral cavity.

Blood sample and cytobrush sample at inclusion and before anti-cancer treatment.

Healthy oral mucosa will be collected using a cytobrush, which is a minimally invasive method for patients

Cytobrush sample

Blood sampling (6 mL), taken from a routine biological exam

Blood sampling

Philippe Zrounba, M.D.

Pierre Martinez, Ph.D.

The goal of this project is to describe somatic mutations of healthy oral mucosa from patients with oral squamous cell carcinoma (OSCC).

Epidermoid carcinomas of upper aerodigestive tract are the 8th most common cancers in the world. Worldwide, this represents more than 500.000 cases per year and 20.000 cases per year in France (statistics 2018-2020). Among these cancers, oral squamous cell carcinoma (OSCC) are the most common location, leading to significant morbidity and mortality.

Despite recent advances in diagnosis, treatment and monitoring, the overall 5-year survival rate of patients with epidermoid carcinomas of upper aerodigestive tract has not improved significantly and remains around 40-50 % for all combined locations. These pejorative survival rates, as well as the increase in the incidence of these cancers, have not changed much over the past 30 years. This situation can be attributed in part to a diagnosis too late. Indeed, only 1/3 of patients with high-risk squamous cell carcinoma of the head and neck are diagnosed at an early stage. This issue of early diagnosis is mainly due to the lack of suitable screening and diagnostic biomarkers. Beyond diagnosis, the identification of biomarkers is also a prognostic and predictive interest since they could predict the course of the disease as well as the response to treatment.

"Drivers" mutations, with oncogenic potential, can be present from the very early stages of epidermoid carcinomas of upper aerodigestive tract and therefore constitute potential biomarkers. However, recent studies have demonstrated the presence of driver mutations in different types of oral cavity's healthy tissue, some being even associated with a protective effect against tumor initiation. In order to improve prevention and early diagnosis of OSCC, it is important to better understand the evolutionary dynamics of somatic mutations in the oral mucosa, which is still poorly characterized.

A clinical-biological cohort of patients with epidermoid carcinomas of the oral cavity.

Blood sample and cytobrush sample at inclusion and before anti-cancer treatment.

Tobacco, Alcohol and Cancerization of the Oral Mucosa (TACO)

Clinical-biological, Prospective, Monocentric Cohort Study to Describe Somatic Mutations in Healthy Oral Mucosa From Patients With Oral Squamous Cell Carcinoma (OSCC)

Selective advantage of the 62 driver genes already identified

Selective advantage of non-driver OSCC genes

Identified mutations described by type and number

Correlation between tobacco consumption and total number of somatic mutations detected

Correlation between alcohol consumption and total number of somatic mutations

Centre Leon Berard

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Diseases

Women undergoing clinically-indicated hysterectomy for endometrial cancer or precursors

Women undergoing clinically-indicated hysterectomy for benign conditions

Rebecca C Arend, MD

Megan A Clarke-Corso, Ph.D.

Warner Huh

Background:

Endometrial cancer is a common and deadly cancer for women. It is getting more common and deadly because risk factors like age and obesity are increasing. It is highly curable if it is identified early. But there may be no symptoms early or they may be missed. Also, this cancer is becoming more common and deadly for black women than white women. Researchers want to find better ways to take samples and test them for this cancer. They want to study this for a racially diverse population. One way to take samples might be from a tampon.

Objective:

To see if it is possible and acceptable to collect an endometrial sample from women by using a tampon placed in the vagina.

Eligibility:

Women at least 45 years old who are having a hysterectomy

Design:

Participants will put a tampon in their vagina at least 30 minutes before their surgery.

Participants will take a short survey.

The tampon will be collected during the surgery.

A small piece of tissue will be collected from the uterus that is removed in surgery.

Participants will give a blood sample.

Before or after surgery, participants will answer questions. These will be about their medical history and basic data such as age and race.

Researchers will follow participants medical records for up to 3 years after the study.

Researchers will study the samples and tampons. They will compare how well cancer and other markers are detected between the samples.

BACKGROUND:

* Endometrial cancer is the most common and second deadliest gynecological cancer in women in the United States, with over 63,000 new cases and 11,000 deaths expected to occur in 2018. Unlike most cancers, endometrial cancer incidence and mortality are increasing, due to increases in risk factors such as obesity and population aging.
* Racial disparities in endometrial cancer incidence and mortality have been reported, with black or African American (henceforth referred to as black ) women experiencing more rapid increases in incidence, as well as a higher burden of endometrial cancer mortality compared to other racial/ethnic groups. The underlying basis for these disparities is likely multifactorial, involving biological differences, as well as clinical factors related to access to care, delayed diagnosis, and differences in treatment and surgical management.
* If identified early, endometrial cancer can be highly curable; however, the earliest stages may be asymptomatic, and clinical symptoms are often missed. Combining sensitive molecular testing approaches with non-invasive sampling techniques may to lead to the development of novel endometrial cancer early detection approaches with the potential to overcome disparities in access to care and time to diagnosis and treatment. We and others have recently shown that vaginal tampons offer an acceptable and feasible method for identifying molecular markers with high sensitivity and specificity for endometrial cancer. Importantly, these proof-of-principle studies have been conducted in predominantly non-Hispanic white (white) populations, and studies of molecular markers for endometrial cancer, including those involving vaginal tampons, are lacking in black women.

OBJECTIVES:

-The goal of this study is to evaluate the acceptability, feasibility, and clinical performance of vaginal tampon sampling for molecular testing of endometrial cancer early detection biomarkers in a racially diverse clinical population.

ELIGIBILITY:

-Eligible participants will include women aged greater than or equal to 45 years undergoing clinically-indicated hysterectomy for endometrial cancer, endometrial cancer precursors, or benign conditions at the University of Alabama s Division of Gynecologic Oncology.

DESIGN:

* This is a case-control study with prospective follow-up of the electronic health record or up to 3 years. Cases will be defined as women with histologically-confirmed endometrial cancer or cancer precursors diagnosed at hysterectomy. Controls will have no histologic evidence of endometrial cancer or endometrial cancer precursors diagnosed at hysterectomy.
* The primary endpoints of this study will be: 1) The acceptability and feasibility of vaginal tampon sampling in a racially diverse clinical population, assessed by evaluating approximately 10 items from a brief survey regarding tampon sampling and the DNA yield from the vaginal tampon, respectively and 2) The prevalence, sensitivity, and specificity of endometrial cancer driver mutations in tampon and tissue samples in cases and controls.

The DETECT Study: Discovery and Evaluation of Testing for Endometrial Cancer in Tampons

Women with histologically confirmed diagnosis of endometrial cancer

Women with histologically confirmed diagnosis of precursors (e.g., atypical hyperplasia)

Women with fibroids, polyps, endometrial hyperplasia without atypia, adenomyosis, normal endometrium, or other benign conditions determined by histology and/or clinical imaging.

Women will be given a 10 question survey to assess acceptability of tampon sampling

The feasibility of tampon sampling will be determined by successful tampon insertion according to protocol prior to surgery and sufficient DNA yield (e.g., 1-2 microgram) from the tampon sample.

National Cancer Institute (NCI)

University of Alabama at Birmingham

Associate Professor

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Participants must not be under investigation for any pre-cancerous or cancerous lesions of the genital tract, and must be scheduled for a hysterectomy, bilateral salpingectomy with/without bilateral oopherectomy for presumed benign condition.

Dr Ioannis Ragoussis, PhD

This study aims to develop and validate a test for diagnosing ovarian and endometrial cancers early. It relies on detecting somatic mutations that are associated with these cancers in a biofluids sample taken from the cervix and the uterine cavity.

For women in high-income countries, ovarian/fallopian tube and endometrial cancers are within the top four cancers in terms of incidence, death and healthcare expenditure. The deaths associated with these cancers are largely caused by stage III/IV disease, for which cure rates have not changed in three decades, despite escalating costs of treatment. Attempts at early diagnosis have been ineffective in reducing mortality, because the high-grade subtypes, which account for the majority of deaths, metastasize while the primary cancer is still small, has not caused symptoms, and is undetectable by imaging or blood tumour markers.

In recent years, the recognition that somatic mutations are early steps in carcinogenesis has led to a shift from tests such as imaging and non-specific blood tumour markers to technology that detects cancer-associated mutations in cervical, uterine, or blood samples. Several DNA-tagging technologies have been shown to be capable of identifying small amount of cancer DNA among thousands of normal cells, the proverbial needle in a haystack.

This investigation aims to develop and validate an in-house developed DNA tagging technology 'DOvEEgene-Haloplex' for the early diagnosis of endometrial and ovarian cancers. The assay pipeline for barcoding and agnostic testing of the biofluids must lend itself to automation and high throughput testing. It must have good sensitivity and more importantly very high specificity, as the only way to corroborate a positive test is to remove the uterus, tubes and ovaries.

DOvEEgene: Diagnosing Ovarian and Endometrial Cancer Early Using Genomics

Diagnosis ovarian and endometrial cancers by detection of cancer-related mutation taken by brush sample of uterus with high sensitivity and specificity.

Pain scores reported by participants on numeric pain and discomfort scale (NPS). Patients' attitude towards the test including willingness to have it done on an annual basis will be evaluated.

Evaluate all risks associated with the DOvEEgene test including complications from the sampling technique as well as unnecessarily interventions resulting from false positive tests.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An European Platform for Translational Research in Myelodysplastic Syndromes	NCT04174547	Myelodysplastic...		18 Years -	Istituto Clinico Humanitas
Characterization & Comparison of Drugable Mutations in Primary and Metastatic Tumors, CTCs and cfDNA in MBCpatients	NCT02626039	Metastatic Brea...		18 Years -	Hospital General Universitario Gregorio Marañon
Mechanisms of Somatic Mutation and Tumor Initiation in Pre-malignant Kidney Tubule Cells	NCT06194669	Carcinoma, Rena... Von Hippel-Lind...	Blood and urine...	18 Years -	IRCCS San Raffaele
DOvEEgene Fleur: New Uterine Sampling Tool	NCT04258449	Women With Susp...	DOvEEgene Fleur...	18 Years -	McGill University
Tobacco, Alcohol and Cancerization of the Oral Mucosa (TACO)	NCT06425146	Oral Squamous C...	Cytobrush sampl... Blood sampling	18 Years -	Centre Leon Berard
The DETECT Study: Discovery and Evaluation of Testing for Endometrial Cancer in Tampons	NCT03538665	Endometrial Can... Endometrial Can...		45 Years - 99 Years	University of Alabama at Birmingham
DOvEEgene Fleur: New Uterine Sampling Tool	NCT04258449	Women With Susp...	DOvEEgene Fleur...	18 Years -	McGill University
Characterization & Comparison of Drugable Mutations in Primary and Metastatic Tumors, CTCs and cfDNA in MBCpatients	NCT02626039	Metastatic Brea...		18 Years -	Hospital General Universitario Gregorio Marañon
DOvEEgene: Diagnosing Ovarian and Endometrial Cancer Early Using Genomics	NCT02288676	Ovarian Neoplas... Endometrial Neo... Endometrial Can... Ovarian Cancer Screening Safety Reduced Mortali... Reduced Morbidi... Early Diagnosis		18 Years -	McGill University

Spots Global Cancer Trial Database for somatic mutations