Genetic Mutations in B-Acute Lymphoblastic Leukemia Among African American and European American Children
| Autor: | Christian R. Gomez, Gail Megason, Eldrin Bhanat, Teja Poosarla, Yunyun Zhou, Jason Schallheim, Amit Reddy, Ingrid Espinoza, Dana Cole, Jovanny Zabaleta |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Adolescent Biopsy medicine.disease_cause Polymorphism Single Nucleotide White People 03 medical and health sciences 0302 clinical medicine Germline mutation Bone Marrow Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Internal medicine Genetic variation Biomarkers Tumor medicine Humans Genetic Predisposition to Disease B Acute Lymphoblastic Leukemia Child Germ-Line Mutation Exome sequencing Mutation Whole Genome Sequencing business.industry Age Factors Computational Biology Disease Management Infant Cancer Hematology medicine.disease Black or African American Gene expression profiling Leukemia 030104 developmental biology Child Preschool Population Surveillance 030220 oncology & carcinogenesis Female business |
| Zdroj: | Clinical Lymphoma Myeloma and Leukemia. 18:e501-e508 |
| ISSN: | 2152-2650 |
| DOI: | 10.1016/j.clml.2018.08.003 |
| Popis: | Background The survival of patients with B-acute lymphoblastic leukemia (B-ALL) is significantly lower in African American (AA) children compared with European American children (EA). Here, we present a whole exome sequencing (WES) study showing race-specific genetic variations that may play a role on the disparate outcomes among AA and EA children with B-ALL. Patients and Methods Five AA and 15 EA patients ranging in age from 1 to 18 years were enrolled. The median blast percentage was 94.8% (range, 64.5%-99.9%). Frozen bone marrow aspirate was used to extract DNA, and WES was performed, focusing on race and B-ALL-specific germline mutations. Results Most genetic variants (n = 339) were shared between AA and EA children. Some genetic aberrations were only uniquely identified in AA (n = 58) and others in EA (n = 52) In AA, the genetic aberrations clustered in canonical pathways related to telomerase signaling and cancer signaling. In EA, the unique genetic aberration clustered in pathways related to stem cell pluripotency and hereditary cancer. Conclusions Our study revealed aberrant genetic aberrations in signaling networks that may contribute to race-specific aspects of leukemogenesis. Our results suggest the value of WES as a tool for development of individual gene signatures and gene scores for AA and EA children afflicted by B-ALL. These findings may ultimately impact disease management and contribute to the elimination of disparate outcomes in AA children with B-ALL. |
| Databáze: | OpenAIRE |
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