Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment.

Pediatric adrenocortical tumors (ACTs) are rare and heterogeneous. Approximately 50% of children with ACT carry a germline variant; however, the genetic underpinning of remaining cases has not been elucidated. In patients having germline variants, loss of maternal chromosome 11 and duplication of the paternal copy [paternal uniparental disomy, (UPD)] occurs early in tumorigenesis and explains the overexpression of , the hallmark of pediatric ACT. Beckwith-Wiedemann syndrome (BWS) is also associated with overexpression of due to disruption of the 11p15 loci, including segmental UPD. Here, we report six children with ACT with wild type and germline paternal 11p15 UPD. Median age of five girls and one boy was 3.2 years (range 0.5-11 years). Two patients met the criteria for BWS before diagnosis of ACT. However, ACT was the first and only manifestation of paternal 11p15 UPD in four children. Tumor weight ranged from 21.5 g to 550 g. Despite poor prognostic features at presentation, such as pulmonary metastasis, bilateral adrenal involvement, and large tumors, all patients are alive 8-21 years after cancer diagnosis. Our observations suggest that children with ACT and wild type , irrespective of their age, should be screened for germline abnormalities in chromosome 11p15.