A5074963110- Acute Myeloid Leukemia Research
- Childhood Cancer Survivors' Quality of Life
- Acute Lymphoblastic Leukemia research
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Neutropenia and Cancer Infections
- Lung Cancer Treatments and Mutations
- Hematological disorders and diagnostics
- Single-cell and spatial transcriptomics
- Genetics and Neurodevelopmental Disorders
- Family Support in Illness
- Health, Environment, Cognitive Aging
- RNA modifications and cancer
- DNA Repair Mechanisms
- Multiple and Secondary Primary Cancers
- Neuroblastoma Research and Treatments
- Cancer Research and Treatments
- Cancer Risks and Factors
- Glioma Diagnosis and Treatment
- Virus-based gene therapy research
- Science, Research, and Medicine
- Hematopoietic Stem Cell Transplantation
- Chemotherapy-induced cardiotoxicity and mitigation
St. Jude Children's Research Hospital
2020-2025
Abstract We present the first comprehensive investigation of clonal hematopoiesis (CH) in 2,860 long-term survivors pediatric cancer with a median follow-up time 23.5 years. Deep sequencing over 39 CH-related genes reveals mutations 15% survivors, significantly higher than 8.5% 324 community controls. CH is associated exposures to alkylating agents, radiation, and bleomycin. Therapy-related shows significant enrichment STAT3, characterized as gene specific Hodgkin lymphoma, TP53. Single-cell...
Mounting evidence supports the occurrence of accelerating aging among long-term survivors childhood cancer. We aimed to investigate epigenetic age acceleration (EAA) in and evaluate associations between EAA, treatment exposures, health behaviors, chronic conditions (CHCs).Genome-wide methylation data were generated with Infinium EPIC BeadChip on blood-derived DNA from 2139 282 frequency matched controls St Jude Lifetime Cohort Study. EAAs estimated as residuals a linear regression (Levine's...
Abstract Retinoic acid (RA) is a standard-of-care neuroblastoma drug thought to be effective by inducing differentiation. Curiously, RA has little effect on primary human tumors during upfront treatment but can eliminate cells from the bone marrow post-chemo maintenance therapy—a discrepancy that never been explained. To investigate this, we treat large cohort of cell lines with and observe most RA-sensitive predominantly undergo apoptosis or senescence, rather than We conduct genome-wide...
Abstract Purpose: The purpose of the study was to design a pan-cancer gene panel for childhood malignancies and validate it using clinically characterized patient samples. Experimental Design: In addition 5,275 coding exons, SJPedPanel also covers 297 introns fusions/structural variations 7,590 polymorphic sites copy-number alterations. Capture uniformity limit detection are determined by targeted sequencing cell lines dilution experiment. We its coverage in silico analysis an established...
Abstract While >85% of children with cancer will become five-year survivors, they are at substantially increased risk developing subsequent neoplasms (SNs) in part due to DNA-damaging therapy. However, the effects primary therapy on SN genomic landscape unknown. We utilized biospecimens collected through Childhood Cancer Survivor Study (CCSS) and employed whole-genome, exome, RNA sequencing analyze 199 SNs (median diagnosis age 37.8 years, range 13.0-54.4) matched germline tissue from...
Adult survivors of childhood cancer are at increased risk cardiac late effects.
<div>Abstract<p>We present the first comprehensive investigation of clonal hematopoiesis (CH) in 2,860 long-term survivors pediatric cancer with a median follow-up time 23.5 years. Deep sequencing over 39 CH-related genes reveals mutations 15% survivors, significantly higher than 8.5% 324 community controls. CH is associated exposures to alkylating agents, radiation, and bleomycin. Therapy-related shows significant enrichment <i>STAT3</i>, characterized as gene...
Abstract Background: Extensive efforts in the past decade have revolutionized our understanding of genetic underpinnings childhood malignancies and identified numerous driver alterations that can provide potential targets for novel therapy are excellent biomarkers disease monitoring. For these purposes, a whole genome or exome sequencing approach be resource prohibitive. Numerous gene panels developed adult cancers to address challenges. Due dramatic differences landscapes between pediatric...
<p>Figure S1: Age distribution of the cohort. Figure S2: The bleomycin 3rd tertile. S3: Distribution cancer types treated without alkylating agents, platinum, anthracyclines, bleomycin, dactinomycin, epipodophyllotoxins, methotrexate, vinca alkaloids. S4: Conceptual illustration for age- and therapy-related clonal hematopoiesis. S5: cell phenotypes harboring STAT3 Y640F mutation. S6: Regression analysis on public dataset to reproduce clone expansion pattern in main 4A. S7: Longitudinal...
<div>Abstract<p>We present the first comprehensive investigation of clonal hematopoiesis (CH) in 2,860 long-term survivors pediatric cancer with a median follow-up time 23.5 years. Deep sequencing over 39 CH-related genes reveals mutations 15% survivors, significantly higher than 8.5% 324 community controls. CH is associated exposures to alkylating agents, radiation, and bleomycin. Therapy-related shows significant enrichment <i>STAT3</i>, characterized as gene...
<p>Table S2: List of CH mutations identified. Table S7: Mutations analyzed in serial analysis. S8: Clinical features the survivors. S9: primers used ddPCR validation.</p>
<p>Table S2: List of CH mutations identified. Table S7: Mutations analyzed in serial analysis. S8: Clinical features the survivors. S9: primers used ddPCR validation.</p>
<p>Figure S1: Age distribution of the cohort. Figure S2: The bleomycin 3rd tertile. S3: Distribution cancer types treated without alkylating agents, platinum, anthracyclines, bleomycin, dactinomycin, epipodophyllotoxins, methotrexate, vinca alkaloids. S4: Conceptual illustration for age- and therapy-related clonal hematopoiesis. S5: cell phenotypes harboring STAT3 Y640F mutation. S6: Regression analysis on public dataset to reproduce clone expansion pattern in main 4A. S7: Longitudinal...
<p>Figure S1: Age distribution of the cohort. Figure S2: The bleomycin 3rd tertile. S3: Distribution cancer types treated without alkylating agents, platinum, anthracyclines, bleomycin, dactinomycin, epipodophyllotoxins, methotrexate, vinca alkaloids. S4: Conceptual illustration for age- and therapy-related clonal hematopoiesis. S5: cell phenotypes harboring STAT3 Y640F mutation. S6: Regression analysis on public dataset to reproduce clone expansion pattern in main 4A. S7: Longitudinal...
<p>Table S2: List of CH mutations identified. Table S7: Mutations analyzed in serial analysis. S8: Clinical features the survivors. S9: primers used ddPCR validation.</p>
<p>Figure S1: Age distribution of the cohort. Figure S2: The bleomycin 3rd tertile. S3: Distribution cancer types treated without alkylating agents, platinum, anthracyclines, bleomycin, dactinomycin, epipodophyllotoxins, methotrexate, vinca alkaloids. S4: Conceptual illustration for age- and therapy-related clonal hematopoiesis. S5: cell phenotypes harboring STAT3 Y640F mutation. S6: Regression analysis on public dataset to reproduce clone expansion pattern in main 4A. S7: Longitudinal...
<p>Table S2: List of CH mutations identified. Table S7: Mutations analyzed in serial analysis. S8: Clinical features the survivors. S9: primers used ddPCR validation.</p>
<div>Abstract<p>We present the first comprehensive investigation of clonal hematopoiesis (CH) in 2,860 long-term survivors pediatric cancer with a median follow-up time 23.5 years. Deep sequencing over 39 CH-related genes reveals mutations 15% survivors, significantly higher than 8.5% 324 community controls. CH is associated exposures to alkylating agents, radiation, and bleomycin. Therapy-related shows significant enrichment <i>STAT3</i>, characterized as gene...
Abstract Background Large scale genomics projects have identified driver alterations for most childhood cancers that provide reliable biomarkers clinical diagnosis and disease monitoring using targeted sequencing. However, there is lack of a comprehensive panel matches the list known genes. Here we fill this gap by developing SJPedPanel cancers. Results covers 5,275 coding exons 357 genes, 297 introns frequently involved in rearrangements generate fusion oncoproteins, commonly...
Abstract Background: The epigenetic clock becomes an important biomarker in aging research, where age (EA) approximates chronological with high accuracy and acceleration (EAA) demonstrates superior performance predicting health outcomes the general population. utility of EAA among adult survivors childhood cancer is largely unknown. We aimed to compare between non-cancer controls, evaluate associations EAA, treatment exposures, behaviors, chronic conditions (CHCs) survivors. Methods:...