ArticleJournal of the National Cancer Institute2015
Germline TP53 variants and susceptibility to osteosarcoma.
Registry-linked trialAbstract read
In one paragraph
Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04533555 (Randomized Trial of Universal vs. Guideline-directed Germline Testing Among Young Adults With Cancer), which is not on this map. Cited by 78 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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.
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.
Randomized Trial of Universal vs. Guideline-directed Germline Testing Among Young Adults With Cancer
Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Is Our Science Representative? A Systematic Review of Racial and Ethnic Diversity in Orthopaedic Clinical Trials from 2000 to 2020.Clinical orthopaedics and related research · 2022Pooled it
- TP53 Mutations and Survival in Osteosarcoma Patients: A Meta-Analysis of Published Data.Disease markers · 2016Pooled it
- The ENGAGE study: a 3-arm randomized hybrid type 1 effectiveness and implementation study of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic services in childhood cancer survivors.BMC health services research · 2024Trial
- TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Osteosarcoma Across the Age Spectrum: Why Outcomes Diverge and Trials Must Adapt.Journal of clinical medicine · 2026Review
- Population-based genomic detection of childhood cancer predisposition using newborn dried blood spots.Nature communications · 2026Article
- Characterization of putative germline pathogenic variants in 27 candidate cancer-predisposing genes in 813 cats using a feline-specific multiplex targeted sequencing.Scientific reports · 2026Article
- Article
- Understanding and Overcoming Osteosarcoma Heterogeneity.Biomolecules · 2026Review
- Multi-omics analysis reveals the key role of STIL in Li-Fraumeni syndrome and osteosarcoma.NPJ precision oncology · 2026Article
- Phase I/II, open-label, multicenter study of durvalumab in combination with tremelimumab in pediatric patients with advanced solid tumors.Frontiers in oncology · 2026Article
- Article
- Harnessing multi‑omics to revolutionize understanding and management of osteosarcoma: A pathway to precision medicine (Review).International journal of molecular medicine · 2025Review
- Genetic profiling of osteosarcoma in an adolescent using a next‑generation sequencing panel and Sanger sequencing: A case report and review of the literature.Biomedical reports · 2025Article
- Primary hepatic osteosarcoma: a case report and literature review.Frontiers in oncology · 2025Article
- Evaluation of Germline Pathogenic Variant ofAdvanced biomedical research · 2025Article
- Melittin inhibits proliferation, migration, and invasion in osteosarcoma cell lines using 2D and 3D models.The journal of venomous animals and toxins including tropical diseases · 2025Article
- Osteosarcoma: A comprehensive review of model systems and experimental therapies.Medical research archives · 2024Article
- Osteosarcoma through the Lens of Bone Development, Signaling, and Microenvironment.Cold Spring Harbor perspectives in medicine · 2024Review
- POLE2 promotes osteosarcoma progression by enhancing the stability of CD44.Cell death discovery · 2024Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Lisa MirabelloDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB). mirabellol@mail.nih.gov.
Meredith YeagerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Phuong L MaiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Julie M Gastier-FosterDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Richard GorlickDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Chand KhannaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Ana Patiño-GarciaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Luis SierrasesúmagaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Fernando LecandaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Irene L AndrulisDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Jay S WunderDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Nalan GokgozDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Donald A BarkauskasDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Xijun ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Aurelie VogtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Kristine JonesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Joseph F BolandDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Sharon A SavageDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (LM, PLM, SJC, SAS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (MY, XZ, AV, KJ, JFB); Nationwide Children's Hospital and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH (JMGF); Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (RG); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CK); Department Of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain (APG, LS, FL); University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada (ILA, JSW, NG); Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA (DAB).
Funding
NCTN BIQSFP ANBL1531 (NRT)U10CA180886 · NCI · PUBLIC HEALTH INSTITUTE · PI Douglas S. Hawkins · 2014 to 2026
$390.6MSupport for Human Specimen Banking in NCI-Supported Cancer Clinical TrialsU24CA114766 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI RAMIREZ MILAN, NILSA DEL CARMEN · 2005 to 2014
$14.5MCanadian Institutes of Health ResearchIntramural NIH HHSNCI NIH HHS U10 CA180886-01NCI NIH HHS U24 CA114766
Abstract
The etiologic contribution of germline genetic variation to sporadic osteosarcoma is not well understood. Osteosarcoma is a sentinel cancer of Li-Fraumeni syndrome (LFS), in which approximately 70% of families meeting the classic criteria have germline TP53 mutations. We sequenced TP53 exons in 765 osteosarcoma cases. Data were analyzed with χ(2) tests, logistic regression, and Cox proportional hazards regression models. We observed a high frequency of young osteosarcoma cases (age <30 years) carrying a known LFS- or likely LFS-associated mutation (3.8%) or rare exonic variant (5.7%) with an overall frequency of 9.5%, compared with none in case patients age 30 years and older (P < .001). This high TP53 mutation prevalence in young osteosarcoma cases is statistically significantly greater than the previously reported prevalence of 3% (P = .0024). We identified a novel association between a TP53 rare variant and metastasis at diagnosis of osteosarcoma (rs1800372, odds ratio = 4.27, 95% confidence interval = 1.2 to 15.5, P = .026). Genetic susceptibility to young onset osteosarcoma is distinct from older adult onset osteosarcoma, with a high frequency of LFS-associated and rare exonic TP53 variants.
Indexed as
Germ-Line MutationAdultAge of OnsetBone NeoplasmsFemaleGenetic Predisposition to DiseaseHumansLi-Fraumeni SyndromeMaleOsteosarcomaTumor Suppressor Protein p53TP53 protein, humanTumor Suppressor Protein p53
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Registered trials
NCT04533555ClinicalTrials.gov
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.