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Three non-overlapping regions of chromosome arm 11p allele loss identified in infantile tumors of adrenal and liver

✍ Scribed by Jennifer A. Byrne; Lisa A. Simms; Melissa H. Little; Elizabeth M. Algar; Peter J. Smith


Publisher
John Wiley and Sons
Year
1993
Tongue
English
Weight
713 KB
Volume
8
Category
Article
ISSN
1045-2257

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✦ Synopsis


Tumor and constitutional chromosome arm I I p 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 t o 14 chromosome I I 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 I I p within which LOH occurred, which were defined as lying distal t o the gamma-globin locus (I I p I5.5), proximal to the gamma-globin locus but distal t o I I p I 3 (LOH being detected at I I p 15. I ), and restricted t o the I I p I 3 region. Specific LOH within each I I p I5 region was observed in HB, and this represents the first demonstration by a single study of LOH clearly affecting separate regions of chromosome band I I p I 5 in a particular tumor type. One AA showed LOH restricted t o I I p I 3 loci, implicating the involvement of the WTI 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 I I p loci may be significant in the development of tumors which arise in association with BWS.