What drives pediatric Burkitt lymphoma? Timing events in the evolution of cancer using single‐cell whole genome sequencing
نویسندگان
چکیده
Introduction: Burkitt lymphoma (BL) is a rare but highly aggressive B-cell non-Hodgkin lymphoma. BL exhibits characteristic immunophenotype that positive for pan-B cell markers and CD10. The genetic hallmark of the translocation MYC oncogene under regulation an immunoglobulin (IG) heavy or light chain enhancer, resulting in protein overexpression. Notably, by itself not sufficient oncogenesis variety cancer genes are recurrently mutated. can be divided epidemiologically also, more recently, genetically based on driver mutations including DGG-BL (DDX3X, GNA13, GNAI2), IC-BL (ID3 CCND3), Q53-BL (quiet TP53). Despite high survival rates, pediatric patients suffer from long-term side effects relapses usually fatal. In order to develop targeted less toxic therapies, better understanding needed ethology disease. Therefore, our aim characterise cell-of-origin (COO) dissect life history subtypes, pinpointing when during tumorigenesis somatic play role identifying rate-limiting steps malignant transformation. Method: We collected single-cell suspensions patient samples, lymph node biopsies, bone marrow aspirates, as well ascites pleural fluid. To perform flow cytometry, single cells were stained with DAPI panel antibodies: CD10/CD45/CD19 CD10/CD3/CD20. Live B separated DAPI-CD45+ CD19+ DAPI-CD3-CD20+ phenotype. Subsequently, CD10+ CD10- sorted 96-well plates (Figure 1). confirm presence absence IG::MYC PCR was perfomed using patient-specific primers flank locus. Whole genome amplification carried out DNA Primary Template-directed Amplification (PTA) technique subsequently whole sequenced. Results: From sample 4-year-old female we found 1% immune cells, while 17% negative CD10 marker 2A). same patient, 87% 9% 2B). confirmed 2/6 0/6 marrow-derived 3). Keywords: Genomics, Epigenomics, Other -Omics, Non-Hodgkin (Pediatric, Adolescent, Young Adult), Tumor Biology Heterogeneity No conflicts interests pertinent abstract.
منابع مشابه
Whole Genome Sequencing in Cancer Clinics
Patients with a family history of cancer are being evaluated with consistentwith a RTS diagnosis. Themissense variant PRSS1 p.N29I is presingle-gene or gene panel tests (LaDuca et al., 2014). The decreasing cost and potential to provide comprehensive genetic risk assessment makes whole genome sequencing (WGS) an attractive tool for understanding the genetic risk for cancer (Collins and Hamburg,...
متن کاملCancer detection using whole-genome sequencing of cell free DNA
Biomarkers are molecules whose detection provide valuable information regarding human disease. They may herald the presence of a disease or provide information regarding the course of disease and response to treatment. Historically, cancer biomarkers have been based on aberrant protein expression in a subset of tumor types (e.g. CEA in colorectal cancer, PSA in prostate cancer, and CA19-9 in ov...
متن کاملTargeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes.
To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded primary pBL samples. Ninety percent of cases had at least one mutation or genetic alteration, most commonly involving MYC and TP53. EBV(-) cases were more likely than EBV(+) cases to have multiple mutations...
متن کاملDeep Sequencing of MYC DNA-Binding Sites in Burkitt Lymphoma
BACKGROUND MYC is a key transcription factor involved in central cellular processes such as regulation of the cell cycle, histone acetylation and ribosomal biogenesis. It is overexpressed in the majority of human tumors including aggressive B-cell lymphoma. Especially Burkitt lymphoma (BL) is a highlight example for MYC overexpression due to a chromosomal translocation involving the c-MYC gene....
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Hematological Oncology
سال: 2023
ISSN: ['1099-1069', '0278-0232']
DOI: https://doi.org/10.1002/hon.3164_452