Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Aneuploidy

Neoplasm, Residual

Chromosomal Instability

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Neoplastic Processes

Chromosome Aberrations

We will detect cfDNA CIN of multiple myeloma patients who have the curative effect at least very good partial response (VGPR) after front line therapy, and then monitoring cfDNA CIN every two treatment cycles or every three months during follow up，the result will be compared with bone marrow aspiration MFC.

The extracted cfDNA from PB will be analyzed by UCAD to determine the level of CINs

The level of plasma cfDNA CINs

Juan Du, PhD

Ziliang Qian, PhD

Despite the significantly higher complete remission rates and improved survival achieved over the last decade，multiple myeloma (MM) patients continue to relapse due to persistence of minimal residual disease (MRD). Currently, numerous studies have evaluated the prognostic value of MRD by detecting immunophenotypic and immunoglobulin (Ig) gene rearrangements from bone marrow aspiration samples. Here the investigators intend to study the clinical utility of Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) as an MRD assay, which is based on plasma cell-free DNA(cfDNA) low-coverage whole-genome sequencing. UCAD is non-invasive and applicable for tumors with high heterogeneity and extramedullary invasions.

In multiple myeloma, Minimal Residual Disease (MRD) refers to myeloma cells that are present in the bone marrow after a clinical response has been measured and the patient is in remission. A patient who tests "MRD negative" after treatment for myeloma has less than one myeloma cell per million bone marrow cells. Data from recent clinical trials suggest that patients with such a low level of disease may be less likely to experience a relapse of their condition than patients with higher levels. In recent years, MRD testing is now be applied in the management of patients receiving standard therapies for the disease.

Chromosomal instability(CIN) results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related with metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells and cancer cell releasing DNA into peripheral blood (PB) when apoptosis, it is a potentially non-invasive way to detect CIN in PB cfDNA from the MM patients to character MRD level. UCAD is a new method to detecting CIN in the DNA sample from patients, including extracting cfDNA from PB, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of MM patients.

Peripheral blood were collected from MM patients satisfied cohort condition and stored in cell-free DNA-protectant immediately after collection. Cell-free DNA from peripheral blood will be analyzed by Ultrasensitive Chromosomal Aneuploidy Detection

Evaluation of Ultrasensitive Chromosomal Aneuploidy Detection for Detecting Minimal Residual Disease in Multiple Myeloma

Application of Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) as a Surrogate Biomarker of Minimal Residual Diseases for Multiple Myeloma Patients

The patients' prognostic was evaluated with the median time of progress free survival (PFS) and overall survival (OS)

number of patients "declared MRD positive or MRD negative" with the UCAD and MFC test simultaneously among the patients being tested successfully with both

number of patients being tested successfully with the UCAD among the patients included in this cohort

The MRD negative patients accounted for the total enrollment

Shanghai Changzheng Hospital

Deputy director of hematology

Diseases and Abnormalities at or Before Birth

Carcinoma

Carcinoma, Transitional Cell

Congenital Abnormalities

Chromosome Disorders

Neoplasms, Glandular and Epithelial

Genetic Diseases, Inborn

Transitional Cell Carcinoma

Pre-surgery patients with urothelial carcinoma will be the experimental group to determine the sensitivity and specificity of UCAD analysis, the result will be compared with cytology and FISH.

Patients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UCAD analysis.

The level of CIN The extracted DNA from morning urine will be analyzed by UCAD to determine the level of CIN.

Low-coverage whole-genome sequencing of urine exfoliated cells

Shuxiong zeng, M.D., Ph.D

Shuxiong Zeng, M.D. Ph.D

Chuangliang Xu, M.D., Ph.D

Chromosomal instability (CIN) refers to ongoing chromosome segregation errors throughout consecutive cell divisions. CIN is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. Analyzing CIN of the DNA extracted from urothelial cells in urine samples seems a promising method for diagnosing, monitoring, and predicting the prognosis of bladder cancer patients. CIN can be assessed using experimental techniques such as bulk DNA sequencing, fluorescence in situ hybridization (FISH), or conventional karyotyping. However, these techniques are either time-consuming or non-specific. We here intend to study whether a new method named Ultrasensitive Chromosomal Aneuploidy Detection (UCAD), which is based on low-coverage whole-genome sequencing, can be used to analyze CIN thus help diagnosing and treating bladder cancer patients.

CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related with metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells, it is a potentially non-invasive way to detect CIN in the urothelial cells from the urine sample for diagnosing and monitoring bladder cancer patients. UCAD is a new method to detecting CIN in the DNA sample from patients, including extracting DNA from urine, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of bladder cancer patients.

The investigators intended to conduct a prospective study by analyzing urine samples from bladder cancer patients and control groups that without any tumor in the urinary system or other organs to compare the specificity and sensitivity of UCAD test for diagnosing urothelial carcinoma to other modalities, such as urine cytology or fluorescence in situ hybridization (FISH).

DNA from Urine Exfoliated Cells will be analyzed by Ultrasensitive Chromosomal Aneuploidy Detection

Application of UCAD for Diagnosing Urothelial Carcinoma.

Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) in Urine Exfoliated Cells for Diagnosis of Urothelial Carcinoma in in Urine Exfoliated Cells

We will try to protect the information of the included participants

Level of CIN in the urine sample compared with the grade of the tumor confirmed by histopathologic examination

Level of CIN in the urine sample compared with the stage of the tumor confirmed by histopathologic examination.

Number of patients "declared positive" with the UCAD test among the patients suffered from urothelial carcinoma.

Number of patients "declared negative" with the UCAD test among the patients without cancer.

Number of patients "declared positive" with the UCAD analysis versus patients "declared positive" with the urine cytology.

Number of patients "declared negative" with the UCAD analysis versus patients " declared negative " with the urine cytology.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Ultrasensitive Chromosomal Aneuploidy Detection for Detecting Minimal Residual Disease in Multiple Myeloma	NCT04122092	Multiple Myelom...	The level of pl...	18 Years -	Shanghai Changzheng Hospital
Application of UCAD for Diagnosing Urothelial Carcinoma.	NCT03998371	Urothelial Carc... Diagnoses Disea... Chromosomal Abn... Urine Marking	Low-coverage wh...	18 Years -	Changhai Hospital
Evaluation of Ultrasensitive Chromosomal Aneuploidy Detection for Detecting Minimal Residual Disease in Multiple Myeloma	NCT04122092	Multiple Myelom...	The level of pl...	18 Years -	Shanghai Changzheng Hospital

Spots Global Cancer Trial Database for chromosomal aneuploidy detection