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By characterizing large numbers of adrnocortical tumor (ACT) cases at the molecular level, we plan to establish the frequency of germline TP53 mutations associated with ACT. We can also establish the frequency of TP53 mutations limited to tumor tissue (somatic). According to limited data publications, the frequency of germline TP53 mutations in children with ACT ranges from 50% to 80%. The reasons for this large range are likely patient selection and small series.
After the amendment to the IPACTR protocol, we have enrolled 73 pediatric patients with ACT. We have collaborations with several countries, including Brazil, Argentina, Honduras, Haiti, Spain, Greece, Saudi Arabia, and England. At St. Jude Children’s Research Hospital, we have processed fresh tumor tissue samples, paraffin blocks, blood, and saliva.
Of our 59 available biological samples, 16 (27%) ACTs had wild-type (WT) TP53 sequences based on genomic DNA. IHC for p53 protein in these WT ACT cases revealed positive IHC for p53 protein in 2 cases, suggesting a mechanism other than a TP53 mutation is responsible for disrupting the TP53 pathway.
The remaining 43 cases had TP53 mutations in genomic DNA. We observed mutations due to changes in one base pair (missense or nonsense mutation), as well as complex mutations (insertion, deletion, and duplication). The picture below illustrates the range of mutations in our cohort.