TY - JOUR
T1 - Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation
AU - Figueiredo, B. C.
AU - Sandrini, R.
AU - Zambetti, G. P.
AU - Pereira, R. M.
AU - Cheng, C.
AU - Liu, W.
AU - Lacerda, L.
AU - Pianovski, M. A.
AU - Michalkiewicz, E.
AU - Jenkins, J.
AU - Rodriguez-Galindo, C.
AU - Mastellaro, M. J.
AU - Vianna, S.
AU - Watanabe, F.
AU - Sandrini, F.
AU - Arram, S. B.I.
AU - Boffetta, P.
AU - Ribeiro, Raul C.
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=30744441388&partnerID=8YFLogxK
U2 - 10.1136/jmg.2004.030551
DO - 10.1136/jmg.2004.030551
M3 - Article
C2 - 16033918
AN - SCOPUS:30744441388
SN - 0022-2593
VL - 43
SP - 91
EP - 96
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 1
ER -