Symptoms and General Pathology

All Conditions

Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Multiple Myeloma

Neoplasms, Plasma Cell

Genetic Predisposition to Disease

Disease Susceptibility

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

This study will involve a single patient group, namely patients with a diagnosis of multiple myeloma diagnosed by a bone marrow aspirate with cytological analysis of the bone marrow smear.Bone marrow samples obtained during the routine follow-up will undergo plasmocyte enrichment using immunopurification using CD138+ beads and nucleic acids will be extracted for sequencing.

The aim of this study is to perform DNA sequencing on abnormal plasmocytes obtained from patients with multiple myeloma, in order to identify alterations which are associated with the existence of this disease. DNA analyses will be performed in a single experiment once all samples have been collected.

DNA sequencing

Charles DUMONTET, Pr

There is a growing body of data suggesting that the the risk of developing multiple myeloma, or myelomagenesis, is associated with genetic alterations occurring in the tumor cells. A limited number of candidate genes and polymorphisms have been reported in patients with this disease. In this study the investigators will compare the genetic information obtained on purified abnormal plasmocytes obtained from patients with multiple myeloma with available public databases in an effort to identify and if possible validate the role of certain mutations and/or polymorphisms in myelomagenesis. Plasmocytes will be obtained by immunomagnetic enrichment using CD138+ beads.

DNA analyses will be performed on purified abnormal plasmocytes, obtained from bone marrow aspirates performed during the standard follow-up of patients with multiple myeloma.

The Aim is to Identify Recurrent Genomic Mutations and/or Predisposing Polymorphisms in Patients With Sporadic Cases of Multiple Myeloma

Analysis of Genomic Alterations in Sporadic Cases of Multiple Myeloma

DNA data acquired in myeloma patient samples will be compared to those of healthy subjects using publically available databases.

Hospices Civils de Lyon

Musculoskeletal Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Osteochondroma

Exostoses, Multiple Hereditary

Osteochondromatosis

Exostoses

Osteophyte

Enchondromatosis

Hyperostosis

Bone Diseases

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Osteochondrodysplasias

Mucopolysaccharidosis IV

Bone Diseases, Developmental

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Hereditary Multiple Osteochondromas

Ollier Disease

Mucopolysaccharidosis Type IV

Christine Alvarez, MD

The purpose of this study is to establish the genetic profile of families in British Columbia with HME.

The purpose of this study is to establish the genetic make-up of families and patients with HME. This will occur as the patient presents to a regular clinic visit. Dr. Alvarez will be introduced to interested patients and their parent(s) and a brief discussion about the project will occur. If the patient and their direct family are interested they will be entered into the study. This will involve interviewing the patients and their direct family. This interview will take about 1 hour. We are interested in identifying all affected family members as far up the family tree as possible. We ask that the idea of the study be introduced to extended family members by the participating family members and then have them call Dr. Alvarez to set up an appointment. Each available member will be interviewed and a physical exam done to determine the location of osteochondromas. In addition, Xrays will be done to determine the location of all osteochondromas. All Xrays will be reviewed. No new ones will be taken unless it is part of the patient's routine care.

To complete the genetic work up DNA analysis will be done on all available family members. This will entail obtaining a blood sample from each family member willing to partake in the study. These blood samples will be used only for the purpose of identifying abnormalities in the genes related to osteochondromas. The blood samples will be taken at British Columbia's Children's Hospital and processed there. DNA samples will be kept confidential.

Establishing the Genetic Profile of Multiple Hereditary Exostoses (HME) in Families of BC

Circle of Care

Vancouver Foundation

Children's & Women's Health Centre of British Columbia

University of British Columbia

Dr. Christine Alvarez

The investigator's goal for this project is to examine the causes of the wide variability of the expression of Hereditary Multiple Exostoses (HME). Previous work completed by our group shows that there exists a correlation between genotype and phenotype such that certain mutations or affected genes cause certain patterns of presentation, symptoms, and signs. The investigators intend to achieve this goal by increasing our study sample size to build upon the results generated from the pilot project of this study, in order to obtain statistical significance. This will be achieved by performing genotype-phenotype analysis on new families presenting with HME in British Columbia.

Subject Recruitment:

New patients presenting with HME will be identified through the offices and clinics of British Columbia Children's Hospital Orthopaedic Department. All potential participants will be educated about the study's rationale, purpose, and procedures and informed consent will be obtained.

Demographics:

All probands (affected patient), their first degree family members and extended family members willing to participate in the study will be interviewed. Information including age, gender, ethnic origin, family history, symptoms, complications and previous surgery will be elucidated.

Phenotype:

Affected patients will have their osteochondroma(s) mapped for location, size, morphology, and symptoms. A total of seventy-five phenotypic parameters divided into four major data categories will be collected. The first two categories are accumulated from physical examinations and include stature and limb segment lengths (15 (x2 for left and right). The other two categories, lesion quality (19 parameters) and limb alignment and deformity (26 parameters) will be drawn from radiographic examinations which are part of the patient's current care. All available xrays will be reviewed and the exostoses characterized radiographically. This will establish the patient's genotype.

Genotype:

Each participant whose genotype is unknown will have a 10 cc. blood sample collected at BC Children's Hospital. This sample will be processed for mutation analysis (DNA extraction from blood samples, mutation analysis) at the Clinical Molecular Diagnostic Laboratory at BC Children's Hospital. The techniques used in the pilot study will be implemented with the exception that microsatellite markers will not be used in order to save cost.

Using EXT 1 and EXT 2 primers (Appendix 1) both strands of a DNA segment are sequenced using ABI Big Dye chemistry Version 2. The resulting sequencing reaction products are then run on an ABI 3100 Avant genetic analyzer. Once a sequence is obtained it is analyzed with SeqScape version 2 software which allows comparison with reference sequence.

Data Analysis:

All information resulting from this research study will be kept strictly confidential. All documents will be identified by an ID number and kept in locked filing cabinets. Participants will not be identified by name in any reports of the completed study. Databases will be stored on project-dedicated laptop computer which is locked in the research office.

The phenotypic data collected will be used to describe family degrees (designed using Cyrillic software), phenotypes of affected individuals and mutations in the exostoses genes of interest (site and type of mutation). Subject heights and segment lengths will be converted to percentile figures to standardize for age and gender to allow for comparison amongst groups.

Genotypic data from the mutation analysis of blood samples will include location of the mutation (early in the gene versus late in the gene), type of mutation (alteration of gene as missense, frameshift, nonsense or splice site), and the amino acid change that was caused by the mutation. The data will be analyzed as follows:

Preliminary Analysis

1. EXT 1 versus EXT 2
2. Males versus Females
3. EXT 1 males versus EXT 1 females versus EXT 2 males versus EXT 2 females

   Secondary Analysis
4. Types of mutations (Missense versus Nonsense versus Splice site versus Frameshift)
5. Early or late mutation (less than 1700 base pairs versus greater than 1700 base pairs)

With 2-way analyses, an unpaired t-test will be calculated and with greater than 2-way analyses, an ANOVA will be calculated. Power will be calculated for every comparison due to the huge variation in sample size. Statistical significance will be set to prior at 0.05 and power of 0.8.

Gene Mutations and Orthopaedic Symptoms Correlation of Multiple Hereditary Exostoses: Multicentre Project

Genotype-Phenotype Correlation of Multiple Hereditary Exostoses: Multicentre Project

Principle Investigator

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Erythroblastic, Acute

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Acute Erythroid Leukemia

Di Guglielmo's Syndrome

Véronique Gelsi-Boyer, MD

Acute erythroid leukemia (AEL) is a morphologically distinct, infrequent (o5%) acute myeloid leukemia (AML) designed as M6 in the French- American-British (FAB) classification. The World Health Organization classification recognizes two subclasses, M6a, a leukemia with myeloid blast cells, and M6b, a very rare, purely erythroid AML. It may be difficult to distinguish between a myelodysplastic syndrome and AEL because of the erythroblastic proliferation, which is increased when dysplasia is present. No recurrent cytogenetic abnormality is specific of AEL and the prognosis is poor with a median survival of 17 months. A study of 14 genes in a series of 92 cases has shown that mutations are frequent in AEL and somewhat differ from the other AMLs by the lower and higher proportion of FLT3-ITD and TP53 mutations, respectively. Only three cases of AEL are reported in the TCGA database. To further characterize AEL, determine whether it constitutes a distinct class of AML and document the reasons for its poor prognosis, the investigators will search for molecular alterations in 40 M6a-AMLs using array comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) of 106 genes known or suspected to have a role in myeloid malignancies or in erythrocyte differentiation.

Molecular Characterization of Acute Erythroid Leukemia (M6-AML) Using Targeted Next-generation Sequencing

Molecular characterization using array comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) of 106 genes known or suspected to have a role in myeloid malignancies or in erythrocyte differentiation.

Institut Paoli-Calmettes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Aim is to Identify Recurrent Genomic Mutations and/or Predisposing Polymorphisms in Patients With Sporadic Cases of Multiple Myeloma	NCT05331313	Multiple Myelom...	DNA sequencing	18 Years -	Hospices Civils de Lyon
Establishing the Genetic Profile of Multiple Hereditary Exostoses (HME) in Families of BC	NCT00473850	Exostoses, Mult...		-	University of British Columbia
Gene Mutations and Orthopaedic Symptoms Correlation of Multiple Hereditary Exostoses: Multicentre Project	NCT00474331	Exostoses, Mult...		-	University of British Columbia
Establishing the Genetic Profile of Multiple Hereditary Exostoses (HME) in Families of BC	NCT00473850	Exostoses, Mult...		-	University of British Columbia
Molecular Characterization of Acute Erythroid Leukemia (M6-AML) Using Targeted Next-generation Sequencing	NCT02861651	Acute Myeloid L...	DNA sequencing	18 Years -	Institut Paoli-Calmettes

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