Assessment of 11p loci status of Simpson-Golabi-Behmel (SGBS) somatic overgrowth syndrome and associated embryonal tumours
- Univ. of Ottawa (Canada)
- Children`s Hospital of Eastern Ontario (Canada)
SGBS, a somatic overgrowth syndrome which we have recently mapped to Xq25-q27, shows significant clinical overlap with the more common Beckwith-Wiedemann syndrome (BWS) including an increased risk of developing embryonal tumors. Two genes from the BWS-linked 11p15 region, IGF2 and H19, are known to undergo parental imprinting. Relaxation of this imprinting has recently been demonstrated in some BWS cases and isolated Wilm`s tumour (WT). Since SGBS and BWS have been postulated to represent distinct defects in a common pathway, we have studied the methylation pattern and transcriptional activity of IGF2 and H19 in isolated SGBS +/- WT tissue. No consistent methylation abnormalities were observed in genomic DNA isolated from SGBS WBC, placenta, fibroblast or cleft lip tissues. Genotyping of H19 cDNA polymorphisms from SGBS fibroblast revealed normal mono-allelic gene expression. IGF2 is currently being analyzed in a similar fashion. It appears that, in distinction from some cases of BWS, abberant 11p15 loci imprinting is not a factor in SGBS pathogenesis in our study population. Furthermore, genotyping with microsatellites in a large SGBS kindred did not reveal inheritance of a common 11p13-15.5 chromosomal region in the 3 children with WT. Loss of heterozygosity (LOH) secondary to a maternal allele duplication was detected in the 11p15.5 loci in the tumor tissue of both SGBS WTs assayed. Thus, while spontaneous relaxation of 11p15 loci imprinting was not observed in either SGBS or SGBS WT, a de facto LOH-based imprinting abnormality is observed in SGBS associated WT. It is unknown if SGBS predisposes renal cells to LOH or confers a cellular selective advantage following LOH or both.
- OSTI ID:
- 133608
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0338
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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