The Brazilian TP53 mutation (R337H) and sarcomas

Autoři: Sahlua Miguel Volc aff001;  Cíntia Regina Niederauer Ramos aff002;  Henrique de Campos Reis Galvão aff001;  Paula Silva Felicio aff002;  Aline Silva Coelho aff002;  Gustavo Noriz Berardineli aff003;  Natalia Campacci aff002;  Cristina da Silva Sabato aff003;  Lucas Faria Abrahao-Machado aff004;  Iara Viana Vidigal Santana aff004;  Nathalia Campanella aff002;  André van Helvoort Lengert aff002;  Daniel Onofre Vidal aff002;  Rui Manuel Reis aff002;  Caio F. Dantas aff008;  Robson C. Coelho aff008;  Erica Boldrini aff005;  Sergio Vicente Serrano aff008;  Edenir Inêz Palmero aff002
Působiště autorů: Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil aff001;  Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil aff002;  Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil aff003;  Pathology Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil aff004;  Barretos Children's Cancer Hospital, Barretos, São Paulo, Brazil aff005;  Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal aff006;  ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal aff007;  Clinical Oncology Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil aff008;  Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, São Paulo, Brazil aff009
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article


Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called “Brazilian germline TP53 mutation” (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients.

Klíčová slova:

Brazil – Breast cancer – Colorectal cancer – Lung and intrathoracic tumors – Mutation databases – Point mutation – Sarcomas – Leiomyosarcoma


1. Fletcher CDM (2013) World Health Organization., International Agency for Research on Cancer. WHO classification of tumours of soft tissue and bone. (4th) IARC Press, Lyon

2. Casali PG, Abecassis N, Bauer S, Biagini R, Bielack S, et al. (2018) Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29: iv51–iv67. doi: 10.1093/annonc/mdy096 29846498

3. Alaggio R, Coffin CM (2015) The Evolution of Pediatric Soft Tissue Sarcoma Classification in the Last 50 Years. Pediatr Dev Pathol 18: 481–494. doi: 10.2350/15-07-1666-MISC.1 26701753

4. Hui JY (2016) Epidemiology and Etiology of Sarcomas. Surg Clin North Am 96: 901–914. doi: 10.1016/j.suc.2016.05.005 27542634

5. Li FP, Fraumeni JF Jr. (1969) Rhabdomyosarcoma in children: epidemiologic study and identification of a familial cancer syndrome. J Natl Cancer Inst 43: 1365–1373. 5396222

6. Schiavi A, Lavigne J, Turcotte R, Kasprzak L, Dumas N, et al. (2015) Using a family history questionnaire to identify adult patients with increased genetic risk for sarcoma. Curr Oncol 22: 317–325. doi: 10.3747/co.22.2588 26628864

7. Achatz MI, Olivier M, Le Calvez F, Martel-Planche G, Lopes A, et al. (2007) The TP53 mutation, R337H, is associated with Li-Fraumeni and Li-Fraumeni-like syndromes in Brazilian families. Cancer Lett 245: 96–102. doi: 10.1016/j.canlet.2005.12.039 16494995

8. Achatz MI, Zambetti GP (2016) The Inherited p53 Mutation in the Brazilian Population. Cold Spring Harb Perspect Med 6.

9. Ribeiro RC, Sandrini F, Figueiredo B, Zambetti GP, Michalkiewicz E, et al. (2001) An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma. Proc Natl Acad Sci U S A 98: 9330–9335. doi: 10.1073/pnas.161479898 11481490

10. Seidinger AL, Mastellaro MJ, Paschoal Fortes F, Godoy Assumpcao J, Aparecida Cardinalli I, et al. (2011) Association of the highly prevalent TP53 R337H mutation with pediatric choroid plexus carcinoma and osteosarcoma in southeast Brazil. Cancer 117: 2228–2235. doi: 10.1002/cncr.25826 21192060

11. Gomes MC, Kotsopoulos J, de Almeida GL, Costa MM, Vieira R, et al. (2012) The R337H mutation in TP53 and breast cancer in Brazil. Hered Cancer Clin Pract 10: 3. doi: 10.1186/1897-4287-10-3 22455664

12. Giacomazzi J, Graudenz MS, Osorio CA, Koehler-Santos P, Palmero EI, et al. (2014) Prevalence of the TP53 p.R337H mutation in breast cancer patients in Brazil. PLoS One 9: e99893. doi: 10.1371/journal.pone.0099893 24936644

13. Villani A, Shore A, Wasserman JD, Stephens D, Kim RH, et al. (2016) Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol 17: 1295–1305. doi: 10.1016/S1470-2045(16)30249-2 27501770

14. Kehdy FS, Gouveia MH, Machado M, Magalhaes WC, Horimoto AR, et al. (2015) Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations. Proc Natl Acad Sci U S A 112: 8696–8701. doi: 10.1073/pnas.1504447112 26124090

15. Custodio G, Taques GR, Figueiredo BC, Gugelmin ES, Oliveira Figueiredo MM, et al. (2011) Increased incidence of choroid plexus carcinoma due to the germline TP53 R337H mutation in southern Brazil. PLoS One 6: e18015. doi: 10.1371/journal.pone.0018015 21445348

16. Pereira R, Phillips C, Pinto N, Santos C, dos Santos SE, et al. (2012) Straightforward inference of ancestry and admixture proportions through ancestry-informative insertion deletion multiplexing. PLoS One 7: e29684. doi: 10.1371/journal.pone.0029684 22272242

17. Saloum de Neves Manta F, Pereira R, Vianna R, Rodolfo Beuttenmuller de Araujo A, Leite Goes Gitai D, et al. (2013) Revisiting the genetic ancestry of Brazilians using autosomal AIM-Indels. PLoS One 8: e75145. doi: 10.1371/journal.pone.0075145 24073242

18. Campanella NC, Berardinelli GN, Scapulatempo-Neto C, Viana D, Palmero EI, et al. (2014) Optimization of a pentaplex panel for MSI analysis without control DNA in a Brazilian population: correlation with ancestry markers. Eur J Hum Genet 22: 875–880. doi: 10.1038/ejhg.2013.256 24193342

19. Falush D, Stephens M, Pritchard JK (2007) Inference of population structure using multilocus genotype data: dominant markers and null alleles. Mol Ecol Notes 7: 574–578. doi: 10.1111/j.1471-8286.2007.01758.x 18784791

20. Karanian M, Coindre JM (2015) [Fourth edition of WHO classification tumours of soft tissue]. Ann Pathol 35: 71–85. doi: 10.1016/j.annpat.2014.11.003 25532684

21. Palmero EI, Schuler-Faccini L, Caleffi M, Achatz MI, Olivier M, et al. (2008) Detection of R337H, a germline TP53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in Southern Brazil. Cancer Lett 261: 21–25. doi: 10.1016/j.canlet.2007.10.044 18248785

22. Garritano S, Gemignani F, Palmero EI, Olivier M, Martel-Planche G, et al. (2010) Detailed haplotype analysis at the TP53 locus in p.R337H mutation carriers in the population of Southern Brazil: evidence for a founder effect. Hum Mutat 31: 143–150. doi: 10.1002/humu.21151 19877175

23. Ognjanovic S, Olivier M, Bergemann TL, Hainaut P (2012) Sarcomas in TP53 germline mutation carriers: a review of the IARC TP53 database. Cancer 118: 1387–1396. doi: 10.1002/cncr.26390 21837677

24. Serrano C, George S (2013) Leiomyosarcoma. Hematol Oncol Clin North Am 27: 957–974. doi: 10.1016/j.hoc.2013.07.002 24093170

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2020 Číslo 1
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