A study of the TP53 Germline Mutation and Clinicopathologic Features in Thai Children with Adrenocortical Carcinoma
Abstract
Material and Methods: This was a retrospective study. From 2009 to 2018, children with ACC from King Chulalongkorn Memorial Hospital and Phramongkutklao Hospital were enrolled into the study. Clinical presentations and hormonal profiles were recorded. Mutation analyses of the TP53 gene were acquired using the next-generation-sequencing method which was performed for germline samples of all patients and the parents of those who tested positive.
Result: Two males and six females with ACC were enrolled into this study. The median age at diagnosis was 25.5 months (range 10 to 67 months). All participants had virilization, either virilization only (n=3) or associated with Cushing (n=5). All participants had had surgery to completely remove all of the tumor and three participants had received adjuvant chemotherapy consisting of etoposide, doxorubicin, and cyclophosphamide. All participants had three different known mutations in the TP53 gene: c.1010G>A (p.R337H), c.916C>T (p.R306*) and c.743G>A (p.R248Q). Two of the three participants with TP53 mutations had pulmonary metastasis. One participant had wild-type TP53 and pulmonary recurrence occurred one year after diagnosis. The median follow-up time was 31 months (range 10 to 168 months. As of this writing, seven participants survived without evidence of recurrence. No second malignancy was found in all participants. One participant who had c.916C>T died of pulmonary metastasis 10 months after diagnosis.
Conclusion: We successfully identified three different germline TP53 mutations in patients with ACC. Progression to pulmonary metastasis and recurrence were higher among participants with TP53 mutations. The treatment outcome of childhood ACC was good when surgery and adjuvant chemotherapy were used.
Keywords
Full Text:
PDFReferences
Ribeiro RC, Michalkiewicz EL, Figueiredo BC, DeLacerda L, Sandrini F, Pianovsky MD, et al. Adrenocortical tumors in children. Braz J Med Res 2000;33:1225-34.
Mahendraraj K, Lau CSM, Sindhu K, Chamberlain RS. Adrenocortical carcinoma in adults and children: a population-based outcomes study involving 1,623 patients from the surveillance, epidemiology, and end result (SEER) database (1973-2012). Clin Surg 2016;1:1–7.
Abiven G, Coste J, Groussin L, Anract P, Tissier F, Legmann P, et al. Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol secreting tumors in a series of 202 consecutive patients. J Clin Endocrionol Metab 2006;91:2650-5.
Sandrini R, Ribeiro RC, DeLacerda L. Extensive personal experience childhood adrenocortical tumor. J Clin Endocrinol Metab 1997;82:2027-31.
Ribeiro RC, Pinto EM, Zambetti GP. Familial predisposition to adrenocortical tumors: clinical and biological features and management strategies. Best Pract Res Clin Endocrinol Metab 2010;24:477–90.
Gonzalez KD, Noltner KA, Buzin CH, Gu D, Wen-Fong CY, Nguyen VQ, et al. Beyond Li Fraumeni syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol 2009;27:1250–6.
Wagner J, Portwine C, Rabin K, Leclerc J, Narod SA, Malkin D. High frequency of germline p53 mutations in childhood adrenocortical cancer. J Natl Cancer Inst 1994;86:1707–10.
Pinto EM, Ribeiro RC, Figueiredo BC, Zambetti GP. Tp53- associated pediatric malignancies. Genes Cancer 2011;2:485– 90.
Choong SS, Latiff ZA, Mohamed M, Lim LLW, Chen KS, Vengidasan L, et al. Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations. Clin Genet 2012;82:564–8.
Herrmann LJ, Heinze B, Fassnacht M, Willenberg HS, Quinkler M, Reisch N, Zink M, Allolio B, Hahner S. TP53 germline mutations in adult patients with adrenocortical carcinoma. J Clin Endocrinol Metab 2012;97:E476-85.
Salmon A, Amikam D, Sodha N, Davidson S, Basel-Vanagaite L, Eeles RA, et al. Rapid development of post-radiotherapy sarcoma and breast cancer in a patient with a novel germline “De-Novo” TP53 mutation. Clin Oncol 2007;19:490–3.
Richard S, Aziz N, Bale S, Bick D, Das S , Gastier-Foster J , et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17: 405-24.
Egoshi K, Masai M, Nagao K, Ito H. 11-Deoxycorticosteroneproducing adrenocortical carcinoma. Urol Int 1999;251–3.
Cecchetto G, Bisogno G, Schneider D, Brecht I, Ganarin A, Bien E, et al. Outcome and prognostic factors in high-risk childhood adrenocortical carcinomas: a report from the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT). Pediatr Blood Cancer 2017;64. doi: 10.1002/pbc. 26368.
Gupta N, Rivera M, Novotny P, Rodriguea V, Bancos I, Lteif A. Adrenocortical carcinoma in children: a clinicopathological analysis of 41 Patients at the Mayo Clinic from 1950 to 2017. Horm Res Paediatr 2018;90:8–18.
Wasserman JD, Novokmet A, Eichler-Jonsson C, Ribeiro RC, Rodriguez-Galindo C, Zambetti GP, et al. Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: a children’s oncology group study. J Clin Oncol 2015;33:602–9.
Petitjean A, Achatz MIW, Borresen-Dale AL, Hainaut P, Olivier M. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene 2007;26:2157–65.
Couch FJ, Shimelis H, Hu C, Hart SN, Lilyquist J, Feng B, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol 2018;3:1190–6.
Ghorayeb N El, Grunenwald S, Nolet S, Primeau V, Côté S, Maugard CM, et al. First case report of an adrenocortical carcinoma caused by a BRCA2 mutation. Med 2016;95. doi: 10.1097/MD.0000000000004756.
Kim H, Doo DC, Choi H. Frequency of pathogenic germline mutation in CHEK2, PALB2, MRE11, and RAD50 in patients at high risk for hereditary breast cancer. Breast Cancer Res Treat 2017;161:95–102.
Xie C, Tanakchi S, Raygada M, Davis JL. Case report of an adrenocortical carcinoma associated with germline CHEK2 mutation. J Endocr Soc 2019;3:284–90.
Varley JM, McGown G, Thorncroft M, James LA, Margison GP, Forster G, et al. Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors. Am J Hum Genet 1999;65:995–1006.
Magnusson S, Gisselsson D, Wiebe T, Kristoffersson U, Borg A, Olsson H. Prevalence of germline TP53 mutations and history of Li-Fraumeni syndrome in families with childhood adrenocortical tumors, choroid plexus tumors, and rhabdomyosarcoma: A population-based survey. Pediatr Blood Cancer 2012;59: 846-53.
Renaux-petel M, Charbonnier F, Théry J, Fermey P, Lienard G, Bou J, et al. Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome. J Med Genet 2018;55:173–80.
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.