Genetic and clinical aspects of paediatric pheochromocytomas and paragangliomas

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art_PETENUCI_Genetic_and_clinical_aspects_of_paediatric_pheochromocytomas_and_2021.PDF (320.44 KB)
Citações na Scopus
11
Tipo de produção
article
Data de publicação
2021
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY
Autores
SOARES, Silvia C.
Citação
CLINICAL ENDOCRINOLOGY, v.95, n.1, p.117-124, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Objective Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL. Patients and Methods This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4-19). The median time of follow-up was 145 months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification and/or target next-generation sequencing panel. Results Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline VHL pathogenic variants, SDHB, SDHD, RET and negative genetic investigation, respectively. Children with germline VHL missense pathogenic variants were younger than those with SDHB or SDHD genetic defects [median (range), 12 (4-16) vs. 15.5 (14-19) years; P = .027]. Moreover, 10 of 11 cases with VHL pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline SDHB pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with SDHD pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL. Conclusions Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with VHL being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.
Palavras-chave
children, genetics, paraganglioma, pheochromocytoma
URI
https://observatorio.fm.usp.br/handle/OPI/41585
Referências
  1. 1000 Genomes Project Consortium, 2015, Nature, V526, P68, DOI 10.1038/nature15393
  2. Barontini M, 2006, ANN NY ACAD SCI, V1073, P30, DOI 10.1196/annals.1353.003
  3. Bausch B, 2014, ENDOCR-RELAT CANCER, V21, P17, DOI 10.1530/ERC-13-0415
  4. Bholah R, 2017, FRONT PEDIATR, V5, DOI 10.3389/fped.2017.00155
  5. Brownstein CA, 2014, GENOME BIOL, V15, DOI 10.1186/gb-2014-15-3-r53
  6. Buffet A, 2019, J CLIN ENDOCR METAB, V104, P1109, DOI 10.1210/jc.2018-02411
  7. Buitenwerf E, 2020, J CLIN ENDOCR METAB, V105, P2381, DOI 10.1210/clinem/dgz188
  8. Cascon A, 2013, ENDOCR-RELAT CANCER, V20, pL1, DOI 10.1530/ERC-12-0339
  9. Curras-Freixes M, 2017, J MOL DIAGN, V19, P575, DOI 10.1016/j.jmoldx.2017.04.009
  10. da Silva TE, 2019, J CLIN ENDOCR METAB, V104, P5923, DOI 10.1210/jc.2019-00984
  11. Dahia PLM, 2020, ENDOCR-RELAT CANCER, V27, pT41, DOI 10.1530/ERC-19-0435
  12. De Krijger RR, 2006, ANN NY ACAD SCI, V1073, P166, DOI 10.1196/annals.1353.017
  13. De Luca A, 2007, J MED GENET, V44, P800, DOI 10.1136/jmg.2007.053785
  14. Eisenhofer G, 2011, ENDOCR-RELAT CANCER, V18, P97, DOI 10.1677/ERC-10-0211
  15. Fagundes GFC, 2019, J ENDOCR SOC, V3, P1682, DOI 10.1210/js.2019-00225
  16. Favier J, 2015, NAT REV ENDOCRINOL, V11, P101, DOI 10.1038/nrendo.2014.188
  17. Fishbein L, 2017, CANCER CELL, V31, P181, DOI 10.1016/j.ccell.2017.01.001
  18. Jha A, 2018, EUR J NUCL MED MOL I, V45, P787, DOI 10.1007/s00259-017-3896-9
  19. Lenders JWM, 2014, J CLIN ENDOCR METAB, V99, P1915, DOI 10.1210/jc.2014-1498
  20. Lerario AM, 2020, CLINICS, V75, DOI 10.6061/clinics/2020/e1913
  21. Li H, 2010, BIOINFORMATICS, V26, P589, DOI 10.1093/bioinformatics/btp698
  22. Martins RG, 2020, CLIN ENDOCRINOL, V92, P545, DOI 10.1111/cen.14184
  23. Naslavsky MS, 2017, HUM MUTAT, V38, P751, DOI 10.1002/humu.23220
  24. Neumann HPH, 2019, JAMA NETW OPEN, V2, DOI 10.1001/jamanetworkopen.2019.8898
  25. Nielsen SM, 2016, J CLIN ONCOL, V34, P2172, DOI 10.1200/JCO.2015.65.6140
  26. Nielsen SM, 2011, AM J MED GENET A, V155A, P168, DOI 10.1002/ajmg.a.33760
  27. Omura M, 2004, HYPERTENS RES, V27, P193, DOI 10.1291/hypres.27.193
  28. Pamporaki C, 2017, J CLIN ENDOCR METAB, V102, P1122, DOI 10.1210/jc.2016-3829
  29. Plouin PF, 2016, EUR J ENDOCRINOL, V174, pG1, DOI 10.1530/EJE-16-0033
  30. Richards S, 2015, GENET MED, V17, P405, DOI 10.1038/gim.2015.30
  31. Richter S, 2013, ADV PHARMACOL, V68, P285, DOI 10.1016/B978-0-12-411512-5.00014-2
  32. Roman-Gonzalez A, 2017, CURR OPIN ENDOCRINOL, V24, P174, DOI 10.1097/MED.0000000000000330
  33. Timmers HJLM, 2007, J CLIN ONCOL, V25, P2262, DOI 10.1200/JCO.2006.09.6297
  34. Tufton N, 2019, ENDOCR CONNECT, V8, P162, DOI 10.1530/EC-18-0522
  35. Vaidya A, 2018, NEW ENGL J MED, V378, P1259, DOI 10.1056/NEJMc1716652
  36. Wang K, 2010, NUCLEIC ACIDS RES, V38, DOI 10.1093/nar/gkq603
  37. Watson IR, 2013, NAT REV GENET, V14, P703, DOI 10.1038/nrg3539
  38. Wong MY, 2019, CLIN ENDOCRINOL, V90, P499, DOI 10.1111/cen.13926
  39. WYSZYNSKA T, 1992, ACTA PAEDIATR, V81, P244, DOI 10.1111/j.1651-2227.1992.tb12213.x
  40. Zhuang ZP, 2012, NEW ENGL J MED, V367, P922, DOI 10.1056/NEJMoa1205119

Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InRad
Artigos e Materiais de Revistas Científicas - LIM/14
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