Evidence map›Paper›PMID 26580448›Full record

ArticleThe New England journal of medicine2015

Germline Mutations in Predisposition Genes in Pediatric Cancer.

Jinghui Zhang, Michael F Walsh, Gang Wu, Michael N Edmonson, Tanja A Gruber, John Easton, Dale Hedges, Xiaotu Ma, Xin Zhou, Donald A Yergeau and 22 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The New England journal of medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 687 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
687citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00137111 phase3completednot on this map

Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia

TypeinterventionalSponsorSt. Jude Children's Research HospitalRan2000 to 2014Enrolled501ConditionsLymphoblastic Leukemia, AcuteArmsPrednisone, Dexamethasone, Vincristine, Daunorubicin, Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase, Methotrexate, Cyclophosphamide, Cytarabine, Etoposide, Mercaptopurine, Imatinib, chemotherapy, intrathecal chemotherapy
3 · Its place in the literature

Who cites it

687 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Potential advantage of clinical exome sequencing inJournal of medical genetics · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Repair of DNA double-strand breaks after low radiation doses in childhood cancer survivors and matched cancer-free individuals.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Characterization of Genetic Etiologic Factors for Pediatric Acute Lymphoblastic Leukemia in Large Childhood Cancer Survivorship Cohorts.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
    Article
  18. Article
  19. Review
  20. Article

627 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors.

Jinghui Zhang *Departments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Michael F Walsh *Departments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Gang Wu *Departments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Michael N EdmonsonDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Tanja A GruberDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
John EastonDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Dale HedgesDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Xiaotu MaDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Xin ZhouDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Donald A YergeauDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Mark R WilkinsonDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Bhavin VadodariaDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Xiang ChenDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Rose B McGeeDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Stacy Hines-DowellDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Regina NuccioDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Emily QuinnDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Sheila A ShurtleffDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Michael RuschDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Aman PatelDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Jared B BecksfortDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Shuoguo WangDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Meaghann S WeaverDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Li DingDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Elaine R MardisDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Richard K WilsonDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Amar GajjarDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
David W EllisonDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Alberto S PappoDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Ching-Hon PuiDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
Kim E Nichols *Departments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).
James R DowningDepartments of Computational Biology (J.Z., G.W., M.N.E., D.H., X.M., X.Z., M.R.W., X.C., M.R., A.P., J.B.B., S.W.), Oncology (M.F.W., T.A.G., R.B.M., S.H.-D., R.N., E.Q., A.G., A.S.P., C.-H.P., K.E.N.), and Pathology (T.A.G., M.R.W., S.A.S., D.W.E., C.-H.P., J.R.D.) and the Pediatric Cancer Genome Project (J.Z., M.F.W., G.W., M.N.E., T.A.G., J.E., X.M., D.A.Y., B.V., X.C., R.B.M., S.H.-D., R.N., E.Q., S.A.S., M.R., A.P., J.B.B., S.W., M.S.W., A.G., D.W.E., A.S.P., C.-H.P., K.E.N., J.R.D.), St. Jude Children's Research Hospital, Memphis, TN; and the Department of Genetics and McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis (L.D., E.R.M., R.K.W.).

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
CANCER SUSCEPTIBILITY VARIANT DISCOVERY IN HIGH THROUGHPUT SEQUENCING DATAR01CA180006 · NCI · WASHINGTON UNIVERSITY · PI DING, LI · 2013 to 2016
$1.1M
NCI NIH HHS CA21765NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA180006
6 · The paper itself

Abstract

backgroundThe prevalence and spectrum of predisposing mutations among children and adolescents with cancer are largely unknown. Knowledge of such mutations may improve the understanding of tumorigenesis, direct patient care, and enable genetic counseling of patients and families.

methodsIn 1120 patients younger than 20 years of age, we sequenced the whole genomes (in 595 patients), whole exomes (in 456), or both (in 69). We analyzed the DNA sequences of 565 genes, including 60 that have been associated with autosomal dominant cancer-predisposition syndromes, for the presence of germline mutations. The pathogenicity of the mutations was determined by a panel of medical experts with the use of cancer-specific and locus-specific genetic databases, the medical literature, computational predictions, and second hits identified in the tumor genome. The same approach was used to analyze data from 966 persons who did not have known cancer in the 1000 Genomes Project, and a similar approach was used to analyze data from an autism study (from 515 persons with autism and 208 persons without autism).

resultsMutations that were deemed to be pathogenic or probably pathogenic were identified in 95 patients with cancer (8.5%), as compared with 1.1% of the persons in the 1000 Genomes Project and 0.6% of the participants in the autism study. The most commonly mutated genes in the affected patients were TP53 (in 50 patients), APC (in 6), BRCA2 (in 6), NF1 (in 4), PMS2 (in 4), RB1 (in 3), and RUNX1 (in 3). A total of 18 additional patients had protein-truncating mutations in tumor-suppressor genes. Of the 58 patients with a predisposing mutation and available information on family history, 23 (40%) had a family history of cancer.

conclusionsGermline mutations in cancer-predisposing genes were identified in 8.5% of the children and adolescents with cancer. Family history did not predict the presence of an underlying predisposition syndrome in most patients. (Funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute.).

Indexed as

Genes, NeoplasmGenetic Predisposition to DiseaseGerm-Line MutationAdolescentAutistic DisorderChildFemaleGenes, DominantGenome, HumanHumansMaleNeoplasmsSEER ProgramSequence Analysis, DNAYoung Adult

Identifiers

PMID26580448
PMCPMC4734119

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.