Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations

S. S. Choong, Zarina Abdul Latiff, M. Mohamed, L. L W Lim, K. S. Chen, L. Vengidasan, H. Razali, E. J. Abdul Rahman, H. Ariffin

Research output: Contribution to journalArticle

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Abstract

Li-Fraumeni syndrome (LFS) is a highly penetrant, autosomal dominant disorder where affected individuals carry a 50% risk of developing cancer before 30 years of age. It is most commonly associated with mutations in the tumour suppressor gene, TP53. Adrenocortical carcinoma (ACC) is a very rare paediatric cancer, and up to 80% of affected children are found to carry germline TP53 mutations. Hence, we propose using childhood ACC incidence as selection criteria for referral for TP53 mutation testing, independent of familial cancer history. Under the auspices of the Malaysian Society of Paediatric Haematology-Oncology, four eligible children diagnosed with ACC over a 30-month study period were referred for mutation testing. Three had a germline TP53 mutation. Subsequent TP53 testing in relatives showed two inherited mutations and one de novo mutation. These findings strongly support paediatric ACC as a useful sentinel cancer for initiating a germline TP53/LFS detection programme, particularly in countries where the lack of structured oncogenetic practice precludes the identification of families with LFS features.

Original languageEnglish
Pages (from-to)564-568
Number of pages5
JournalClinical Genetics
Volume82
Issue number6
DOIs
Publication statusPublished - Dec 2012

Fingerprint

Adrenocortical Carcinoma
Germ-Line Mutation
Li-Fraumeni Syndrome
Mutation
Neoplasms
Pediatrics
Hematology
Tumor Suppressor Genes
Patient Selection
Referral and Consultation
cyhalothrin
Incidence

Keywords

  • Childhood adrenocortical carcinoma
  • Germline p53 mutation
  • Li-Fraumeni syndrome
  • P53 tumour suppressor

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations. / Choong, S. S.; Abdul Latiff, Zarina; Mohamed, M.; Lim, L. L W; Chen, K. S.; Vengidasan, L.; Razali, H.; Abdul Rahman, E. J.; Ariffin, H.

In: Clinical Genetics, Vol. 82, No. 6, 12.2012, p. 564-568.

Research output: Contribution to journalArticle

Choong, SS, Abdul Latiff, Z, Mohamed, M, Lim, LLW, Chen, KS, Vengidasan, L, Razali, H, Abdul Rahman, EJ & Ariffin, H 2012, 'Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations', Clinical Genetics, vol. 82, no. 6, pp. 564-568. https://doi.org/10.1111/j.1399-0004.2012.01841.x
Choong, S. S. ; Abdul Latiff, Zarina ; Mohamed, M. ; Lim, L. L W ; Chen, K. S. ; Vengidasan, L. ; Razali, H. ; Abdul Rahman, E. J. ; Ariffin, H. / Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations. In: Clinical Genetics. 2012 ; Vol. 82, No. 6. pp. 564-568.
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