3 NONOVERLAPPING REGIONS OF CHROMOSOME ARM 11P ALLELE LOSS IDENTIFIED IN INFANTILE TUMORS OF ADRENAL AND LIVER

Tumor and constitutional chromosome arm 11p genotypes were compared in 6 hepatoblastoma (HB) patients and 2 adrenal adenoma (AA) patients, with one HB patient and both AA patients displaying clinical features associated with the Beckwith-Wiedemann syndrome (BWS). Using up to 14 chromosome 11 polymorphic markers, loss of constitutional heterozygosity (LOH) was demonstrated in both AA patients and in 4 of 6 HB patients. This identified three distinct and non-overlapping regions of 11p within which LOH occurred, which were defined as lying distal to the gamma-globin locus (11p15.5), proximal to the gamma-globin locus but distal to 11p13 (LOH being detected at 11p15.1), and restricted to the 11p13 region. Specific LOH within each 11p15 region was observed in HB, and this represents the first demonstration by a single study of LOH clearly affecting separate regions of chromosome band 11p15 in a particular tumor type. One AA showed LOH restricted to 11p13 loci, implicating the involvement of the WT1 gene. The second AA patient presented with genitourinary abnormalities and we therefore examined sequences coding for 3 zinc finger domains of WT1 in both AAs. No point mutations were identified in sequence from either patient. Nonetheless our results indicate that 3 separate 11p loci may be significant in the development of tumors which arise in association with BWS. (C) 1993 Wiley-Liss, Inc.