Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation
Open accessAbstract
BACKGROUND: An inherited germline P53 mutation has been identified in cases of childhood adrenocortical carcinoma (ACT), a neoplasm with a high incidence in southern Brazil. The penetrance of ACT in carriers of the point mutation, which encodes an arginine-to-histidine substitution at codon 337 of TP53 (R337H), has not been determined. OBJECTIVE: To investigate the penetrance of childhood ACT in carriers of the R337H TP53 mutation. METHODS: The family histories of 30 kindreds of 41 southern Brazilian children with ACT were obtained. A PCR based assay was used to detect this P53 mutation in a large number of relatives of children with ACT. In all, 927 individuals were tested for the mutation, 232 from the non-carrier and 695 (including the 40 probands) from the carrier parental lines. RESULTS: 40 children with ACT carried the TP53 R337H mutation; the remaining child with ACT was not tested. There was no evidence of Li-Fraumeni syndrome in any of the kindreds; however, seven met the criteria for Li-Fraumeni-like syndrome. The carrier parental line was identified in each kindred. Of the 695 individuals tested in the carrier parental line, 240 (34.5%) were positive for the mutation, while none of the 232 individuals in the other parental line carried the mutation. The penetrance of ACT was 9.9% (95% confidence interval, 8.7% to 11.1%). CONCLUSIONS: The TP53 R337H mutation dramatically increases predisposition to childhood ACT but not to other cancers, and explains the increased frequency of ACT observed in this geographic region.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The high childhood ACC incidence in Southern Brazil is mainly attributed to the high prevalence of the p.R337H low-penetrance allele of TP53.
“This is mainly attributed to the high prevalence of the p.R337H low-penetrance allele of TP53 (6–8).”
From Adrenocortical carcinoma (2014) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Statistical Analysis of Failure Time Data.
Aitkin, M. A., Kalbfleisch, J. D., & Prentice, R. L. (1981) · Biometrics · doi:10.2307/2530581 · Cited by 9,875 · see citing works
Doob, J. L., & Doob, J. L. (1953) · CERN Document Server (European Organization for Nuclear Research) · Cited by 8,964 · see citing works
Germ Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms
Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., et al. (1990) · Science · doi:10.1126/science.1978757 · Cited by 3,765 · see citing works
A cancer family syndrome in twenty-four kindreds.
Li, F. P., Fraumeni, J. F., Mulvihill, J. J., Blattner, W. A., Dreyfus, M., Tucker, M., & Miller, R. (1988) · PubMed · Cited by 1,293 · see citing works
The international incidence of childhood cancer
Parkin, D. M., Stiller, C. A., Draper, G. J., & Bieber, C. A. (1988) · International Journal of Cancer · doi:10.1002/ijc.2910420408 · Cited by 1,022 · see citing works
Ribeiro, R. C., Sandrini, F., Figueiredo, B., Zambetti, G. P., Michalkiewicz, E., Lafferty, A. R., DeLacerda, L., Rabin, M., Cadwell, C., Sampaio, G., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161479898 · Cited by 541 · see citing works
Self-citationMichalkiewicz, E., Sandrini, R., Figueiredo, B., Miranda, E. C. M., Caran, E., Oliveira-Filho, A. G., Marques, R., Pianovski, M. A. D., Lacerda, L., Cristofani, L. M., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.085 · Cited by 519 · see citing works
Self-citationPrevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families
Birch, Hartley, Tricker, Prosser, P., Condie, Kelsey, Harris, Jones, Binchy, Crowther, et al. (1994) · Cancer Research · Cited by 475 · see citing works
Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.
Birch, J. M., Hartley, A. L., Tricker, K. J., Prosser, J., Condie, A., Kelsey, A. M., Harris, M., Jones, P. H. M., Binchy, A., & Crowther, D. (1994) · PubMed · Cited by 421 · see citing works
Tumors associated with p53 germline mutations: a synopsis of 91 families.
Kleihues, P., Schäuble, B., Hausen, A. Z., Estève, J., & Ohgaki, H. (1997) · Europe PMC (PubMed Central) · Cited by 413 · see citing works
Chompret, A., Brugières, L., Abel, A. L. V., Lemerle, J., Ronsin, M., Gardes, M., Dessarps-Freichey, F., Feunteun, J., Hua, D., Ligot, L., et al. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1167 · Cited by 372 · see citing works
A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer
DiGiammarino, E. L., Lee, A. S., Cadwell, C., Zhang, W., Bothner, B. B., Ribeiro, R. C., Zambetti, G. P., & Kriwacki, R. W. (2001) · Nature Structural Biology · doi:10.1038/nsb730 · Cited by 293 · see citing works
Self-citationChildhood Adrenocortical Tumors1
Sandrini, R., Ribeiro, R. C., & DeLacerda, L. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.7.4057 · Cited by 237 · see citing works
Self-citationLatronico, A. C., Pinto, E. M., Domenice, S., Fragoso, M. C. B. V., Martin, R. M., Zerbini, M. C., Lucon, A. M., & Mendonca, B. B. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7957 · Cited by 224 · see citing works
Screening for Retinoblastoma: Presenting Signs as Prognosticators of Patient and Ocular Survival
Abramson, D. H., Beaverson, K. L., Sangani, P. K., Vora, R. A., Lee, T. C., Hochberg, H. M., Kirszrot, J., & Ranjithan, M. (2003) · PEDIATRICS · doi:10.1542/peds.112.6.1248 · Cited by 217 · see citing works
Childhood Adrenocortical Tumors
Sandrini, R. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.7.2027 · Cited by 202 · see citing works
Self-citationThe Codon 47 Polymorphism in p53 Is Functionally Significant
Li, X., Dumont, P., Pietra, A. D., Shetler, C. M., & Murphy, M. E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414637200 · Cited by 119 · see citing works
International Incidence of Childhood Cancer, Vol. II.
(1998) · PubMed · Cited by 34 · see citing works
Competing Risks and Multistate Models
Kalbfleisch, J. D., & Prentice, R. L. (2002) · Wiley series in probability and statistics · doi:10.1002/9781118032985.ch8 · Cited by 31 · see citing works
Longui, C. A., Lemos-Marini, S. H. V., de Figueiredo, B. C., Mendonca, B. B., Castro, M., Liberatore, R. D. R., Watanabe, C., Lancellotti, C. L. P., Rocha, M. N., Melo, M. B., et al. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2004.018978 · Cited by 31 · see citing works
Self-citationAusterlitz, F., & Heyer, É. (1999) · Genetic Epidemiology · doi:10.1002/(sici)1098-2272(1999)16:1 · Cited by 11 · see citing works
6. Markov Chains: Discrete Parameter
(1999) · Society for Industrial and Applied Mathematics eBooks · doi:10.1137/1.9781611971125.ch6 · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Gail MH, Pee D, Benichou J, Carroll R. Designing studies to estimate the penetrance of an identified autosomal dominant mutation: cohort, case- control, and genotyped-proband designs. Genet Epidemiol 1999;16:15-39.
- Chompret A, Brugieres L, Ronsin M, Gardes M, Dessarps-Freichey F, Abel A, Hua D, Ligot L, Dondon MG, Bressac-de Paillerets B, Frebourg T, Lemerle J, Bonaiti-Pellie C, Feunteun J. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer 2000;82:1932-7.
Cited by
Sorted by citations
Else, T., Kim, A. C., Sabolch, A., Raymond, V. M., Kandathil, A., Caoili, E. M., Jolly, S., Miller, B. S., Giordano, T. J., & Hammer, G. D. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1029 · Cited by 892 · see citing works
Custódio, G., Parise, G. A., Kiesel Filho, N., Komechen, H., Sabbaga, C. C., Rosati, R., Grisa, L., Parise, I. Z. S., Pianovski, M. A. D., Fiori, C. M. C. M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.46.3711 · Cited by 201 · see citing works
Self-citationGarritano, S., Gemignani, F., Palmero, E. I., Olivier, M., Martel-Planche, G., Le Calvez-Kelm, F., Brugiéres, L., Vargas, F. R., Brentani, R. R., Ashton-Prolla, P., et al. (2010) · Human Mutation · doi:10.1002/humu.21151 · Cited by 153 · see citing works
<i>TP53</i>Germline Mutations in Adult Patients with Adrenocortical Carcinoma
Herrmann, L. J. M., Heinze, B., Fassnacht, M., Willenberg, H. S., Quinkler, M., Reisch, N., Zink, M., Allolio, B., & Hahner, S. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1982 · Cited by 109 · see citing works
Towards an understanding of the role of p53 in adrenocortical carcinogenesis
Wasserman, J. D., Zambetti, G. P., & Malkin, D. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.09.010 · Cited by 84 · see citing works
Self-citationMolecular epidemiology of adrenocortical tumors in southern Brazil
Custódio, G., Komechen, H., Figueiredo, F. R. O., Fachin, N. D., Pianovski, M. A. D., & Figueiredo, B. C. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.10.019 · Cited by 63 · see citing works
Self-citation
- Authors
- Figueiredo, B. C., Sandrini, R., Zambetti, G. P., Pereira, R. M., Cheng, C., Liu, W., Lacerda, L., Pianovski, M. A., Michalkiewicz, E., Jenkins, J., Rodriguez-Galindo, C., Mastellaro, M. J., Vianna, S., Watanabe, F., Sandrini, F., Arram, S. B. I., Boffetta, P., & Ribeiro, R. C.
- Affiliations
- Hospital de Clínicas Universidade Federal do Paraná (BR)
- St. Jude Children's Research Hospital (US)
- Universidade Federal do Paraná (BR)
- Hospital Erasto Gaertner (BR)
- Centro Infantil Boldrini (BR)
- Centre international de recherche sur le cancer (FR)
- Corresponding author
- Ribeiro, R C
- ORCID
- Figueiredo, B C
- Venue
- Journal of Medical Genetics
- Publisher
- BMJ
- Published
- 2005-07-20
- Volume
- 43
- Issue
- 1
- Pages
- 91-96
- ISSN
- 0022-2593 (ISSN-L)
- 1468-6244
- PMC
- PMC2564508
- OpenAlex
- W2108158811
- Cited by
- 166
- References
- 22
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 10 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 10 · 2015: 11 · 2014: 12 · 2013: 7 · 2012: 12
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Medical Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Funders
- U.S. Department of Health and Human Services
- American Lebanese Syrian Associated Charities (CA 21765)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Institutes of Health (CA21765))
- National Cancer Institute (CA-71907, CA21765, P30CA021765, P01CA071907)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- penetrance, germline TP53 mutation, Li-Fraumeni syndrome, hereditary cancer predisposition, southern Brazil, family history (medicine), mutation carriers
- MeSH terms
- Adrenal Cortex Neoplasms, Child, Child, Preschool, Female, Genotype, Humans, Infant, Male, Pedigree, Risk Factors, Tumor Suppressor Protein p53, Age Distribution, Germ-Line Mutation, Penetrance, Genetic Predisposition to Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
