caa a22 4500 445330597 CHVBK 20180317142736.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s10689-010-9392-z doi (NATIONALLICENCE)springer-10.1007/s10689-010-9392-z Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor [Elektronische Daten] [Emilia Pinto, Raul Ribeiro, Gad Kletter, John Lawrence, Jesse Jenkins, Jinling Wang, Sheila Shurtleff, Lisa McGregor, Richard Kriwacki, Gerard Zambetti] Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome. In fact, about two-thirds of children with ACT have a TP53 mutation. However, less than 10% of pediatric ACT cases occur in Li-Fraumeni syndrome, suggesting that inherited low-penetrance TP53 mutations play an important role in pediatric adrenal cortex tumorigenesis. We identified a novel inherited germline TP53 mutation affecting the acceptor splice site at intron 10 in a child with an ACT and no family history of cancer. The lack of family history of cancer and previous information about the carcinogenic potential of the mutation led us to further characterize it. Bioinformatics analysis showed that the non-natural and highly hydrophobic C-terminal segment of the frame-shifted mutant p53 protein may disrupt its tumor suppressor function by causing misfolding and aggregation. Our findings highlight the clinical and genetic counseling dilemmas that arise when an inherited TP53 mutation is found in a child with ACT without relatives with Li-Fraumeni-component tumors. The Author(s), 2010 Loss of heterozygosity nationallicence Pediatric adrenocortical tumor nationallicence Splice-site mutation nationallicence TP53 nationallicence ACT : Adrenocortical tumor nationallicence DBD : DNA-binding domain nationallicence PCR : Polymerase chain reaction nationallicence IARC : International Agency for Research on Cancer nationallicence NES : Nuclear export signal nationallicence Pinto Emilia International Outreach Program, St. Jude Children's Research Hospital, 262 Danny Thomas Place, 38105-3678, Memphis, TN, USA aut Ribeiro Raul International Outreach Program, St. Jude Children's Research Hospital, 262 Danny Thomas Place, 38105-3678, Memphis, TN, USA aut Kletter Gad Swedish Pediatric Specialty Clinics, Seattle, WA, USA aut Lawrence John Swedish Pediatric Specialty Clinics, Seattle, WA, USA aut Jenkins Jesse Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA aut Wang Jinling Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA aut Shurtleff Sheila Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA aut McGregor Lisa Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA aut Kriwacki Richard Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA aut Zambetti Gerard Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA aut Familial Cancer Springer Netherlands 10/1(2011-03-01), 141-146 1389-9600 10:1<141 2011 10 10689 https://doi.org/10.1007/s10689-010-9392-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-010-9392-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pinto Emilia International Outreach Program, St. Jude Children's Research Hospital, 262 Danny Thomas Place, 38105-3678, Memphis, TN, USA aut NATIONALLICENCE 700 1- Ribeiro Raul International Outreach Program, St. Jude Children's Research Hospital, 262 Danny Thomas Place, 38105-3678, Memphis, TN, USA aut NATIONALLICENCE 700 1- Kletter Gad Swedish Pediatric Specialty Clinics, Seattle, WA, USA aut NATIONALLICENCE 700 1- Lawrence John Swedish Pediatric Specialty Clinics, Seattle, WA, USA aut NATIONALLICENCE 700 1- Jenkins Jesse Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA aut NATIONALLICENCE 700 1- Wang Jinling Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA aut NATIONALLICENCE 700 1- Shurtleff Sheila Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA aut NATIONALLICENCE 700 1- McGregor Lisa Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA aut NATIONALLICENCE 700 1- Kriwacki Richard Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA aut NATIONALLICENCE 700 1- Zambetti Gerard Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/1(2011-03-01), 141-146 1389-9600 10:1<141 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer