title: Characteristic genomic imbalances in pediatric pheochromocytoma.
abstract: Pheochromocytoma (PCC) in children is rare, genetically not well described, and often related to a poor prognosis. We detected genomic imbalances in all 14 tumors from children analyzed by comparative genomic hybridization. A combinatorial loss of chromatin from 3p and 11p was a common feature in 10 of 14 (72%) patients, which was a result of either a loss of a total chromosome 3 and a total chromosome 11 in 6 of 10 patients, or confined deletions of their p arms in 4 of 10 patients. All patients exhibiting a loss of 3p and 11p carried VHL mutations. The VHL mutations were constitutive in 9 cases and somatic and restricted to tumor DNA in the remaining tumor. On the other hand, VHL mutations were absent in 4 patients, 2 who had other familial syndromes (NF1, SDHD) and 2 with unknown etiology. Our data show that the pattern of imbalances in the tumor DNA of PCC patients strongly correlated with an underlying familial VHL mutation. Furthermore, we show that true sporadic PCC is rare in childhood. Thus, children with PCC should be checked for a related predisposing gene. This would also identify familial syndrome patients requiring long-term monitoring for other syndrome-related malignancies.
authors.affiliation: Institute for Human Genetics and Anthropology, UKJ, Jena, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Hering
authors.forename: Monika
authors.initials: M
authors.lastname: Guratowska
authors.forename: Peter
authors.initials: P
authors.lastname: Bucsky
authors.forename: Uwe
authors.initials: U
authors.lastname: Claussen
authors.forename: Jochen
authors.initials: J
authors.lastname: Decker
authors.forename: Guenther
authors.initials: G
authors.lastname: Ernst
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoeppner
authors.forename: Susanne
authors.initials: S
authors.lastname: Michel
authors.forename: Hartmut
authors.initials: H
authors.lastname: Neumann
authors.forename: Thomas
authors.initials: T
authors.lastname: Parlowsky
authors.forename: Ivan
authors.initials: I
authors.lastname: Loncarevic
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002872:Chromosome Deletion; D005260:Female; D042822:Genomic Instability; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization / Q000379:methods; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism