Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation. Issue 1 (20th July 2005)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of medical genetics. Volume 43:Issue 1(2006)
• Page Start: 91
• Page End: 96
• Publication Date: 2005-07-20
• Subjects: ACT, adrenocortical tumour -- LF, Li-Fraumeni syndrome -- MLE, maximum likelihood estimator -- PBL, peripheral blood lymphocytes; TP53 -- penetrance -- adrenocortical tumour -- Li-Fraumeni syndrome -- childhood adrenocortical carcinoma; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2004.030551
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : 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.