Imbalances Of Chromosome Arm 1p In Pediatric And Adult Germ Cell Tumors Are Caused By True Allelic Loss: A Combined Comparative Genomic Hybridization And Microsatellite Analysis

Previous studies on childhood germ cell tumors (GCTs) report highly variable frequencies of losses at chromosome arm I p. Since deletions at I p portend a poor prognosis in other embryonal tumors, this study aims to clarify the question of the frequency of true allelic loss at I p and whether it constitutes a prognostic parameter. We analyzed 13 GCTs from different gonadal and extragonadal sites of children (4 teratomas, 9 malignant GCTs) and 18 GCTs of adolescents and adults (3 teratomas; 15 malignant GCTs) using automated microsatellite analysis with 23 polymorphic markers and chromosomal '' high resolution '' comparative genomic hybridization (HR-CGH). With this combined approach, we detected loss of heterozygosity (LOH) at I p in 8/9 childhood malignant GCTs with concordant data from HR-CGH and microsatellite analyses. In contrast, LOH at I p was not detected in childhood teratomas (0/4) and constituted a rare event in GCTs of adolescence and adulthood (3/18). The commonly deleted region was located at distal 1p36-pter, with a proximal boundary between the markers D1S450 and D1S2870. These data unequivocally demonstrate that deletion at I p is common in childhood GCTs and results in allelic loss. This observation argues for the presence of a classical tumor suppressor at distal I p. Considering the high frequency of LOH at I p and the overall favorable prognosis of childhood GCTs, a prognostic impact of LOH at I p in childhood GCTs appears unlikely. However, since two postpubertal tumors with LOH at I p progressed, a prognostic relevance in this age group seems possible, warranting a prospective evaluation. (c) 2006 Wiley-Liss, Inc.