The Albert Einstein Cancer Center in the Bronx serves a catchment area with large Hispanic and African American minority population. We have conducted several large cohort studies in the Bronx population that demonstrated that prevalence, disease severity and prognosis differ in minority populations for leukemias, myelodysplastic syndromes and anemias(1-6). These studies were conducted by analysis of large cohorts of outcome data stored in the clinical looking glass software developed by Montefiore Medical Center. Furthermore, we have demonstrated that we can conduct large scale cancer specific biomarker on primary patient samples. We recently built a biorepository of samples from 3000+ firefighters who were exposed to the 911 WTC disaster and studied the rates of MGUS and myeloma with proteomic analysis. Using this cohort, we have conducted preliminary studies in 781 individuals that show a significantly increased rate of monoclonal gammopathy (MGUS), a precursor for multiple myeloma in first responder firefighters (Landgren et al, JAMA Oncology, 2018) (7). Furthermore, we have demonstrated capabilities in separating malignant plasma cells from primary myeloma samples (N=50) and using them for epigenomic analysis demonstrating large scale changes in DNA methylation in myeloma (Heuck et al, J Immunol) (8). Having demonstrated our capabilities in conducting epidemiological and biomarker studies, we now propose to comprehensively determine the prevalence, disease characteristics and prognosis of myeloma and precursor lesion (MGUS) in large cohort of minority rich subjects in the Bronx catchment area and create a minority rich database and biorepository for the community.
Aim 1 will determine the prevalence and prognosis of myeloma and precursor MGUS in African American and Hispanic patients and create a comprehensive database using patient cohorts from the last 20 years. We will obtain outcomes from patients consisting of equal numbers of African American, Hispanic and Caucasian subjects. Disease status, Response to treatments and overall survival will be determined in an ethnic specific manner and shared with other investigators.
Aim 2 will build a biorepository of well annotated and genotyped myeloma and MGUS samples from African American and Hispanic subjects: 150 samples from patients with MGUS(N=75) and myeloma (N=75) that will be collected from equal numbers of Hispanic, African American and Caucasian subjects (approximately one third for each group). Serum samples will be used for high resolution proteomic analysis to identify the immunoglobulin subtype. Deep targeted mutational analysis will be conducted. Marrow aspirates will be used for separation of plasma cells (CD138+) that will be used for DNA and RNA for future sequencing and transcriptomic studies. These studies will build a biobank of highly clinically annotated and genotyped samples that will be used for high resolution analysis of genomic differences between myeloma/MGUS between different minority subgroups
Myeloma and its precursor lesion MGUS are found to occur increased incidence in African American subjects. The rates of incidence and overall disease outcomes of these diseases are not very well studied in Hispanics. The proposed studies will assess the epidemiological and molecular characteristics of myeloma and precursor MGUS in African American and Hispanic populations and compare them to Caucasians. We will build a comprehensive large database of myeloma outcomes and also construct a repository of samples from minorities with myeloma and MGUS. The availability of NCORP grant resources as well as a predominant minority population and excellent electronic medical record databases will enable us to successfully complete the proposed studies.
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