Fine mapping of Wilms' tumors with 16q loss of heterozygosity localizes the putative tumor suppressor gene to a region of 6.7 megabases.
BACKGROUND
The aim of this study was to more precisely map the region of 16q loss of heterozygosity (LOH) in Wilms' tumors and to examine the expression of putative tumor suppressor.


METHODS
We performed polymerase chain reaction-based LOH analysis on the 185 sample pairs from 21 to 80 megabases (Mb) on chromosome 16q. Expression of two candidate tumor suppressor genes located within the identified consensus region of 16q LOH was examined by immunohistochemistry.


RESULTS
We identified 16q LOH in 7 (4%) of 185 Wilms' tumors not previously thought to demonstrate such genetic loss. The smallest common region of genetic loss was located between 67.3 and 74.0 Mb on chromosome 16. Within this 6.7-Mb region, there reside only three recognized tumor suppressor genes: E-cadherin, P-cadherin, and E2F4. E-cadherin demonstrates statistically significantly reduced expression in Wilms' tumors with 16q LOH.


CONCLUSIONS
We have localized the consensus region of 16q LOH in Wilms' tumor to a 6.7-Mb locus and have identified three candidate Wilms' tumor suppressor genes within this narrowed region. Our data support E-cadherin as a candidate tumor suppressor gene in Wilms' tumor; however, further studies are needed to definitively prove its role as the tumor suppressor gene associated with 16q LOH.
Safford
Shawn D
SD
Department of Surgery, Division of Pediatric Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Goyeau
Dominique
D
Freemerman
Alex J
AJ
Bentley
Rex
R
Everett
Mary Lou
ML
Grundy
Paul E
PE
Skinner
Michael A
MA
D015820:Cadherins / Q000235:genetics; D002885:Chromosomes, Human, Pair 16; D016147:Genes, Tumor Suppressor; D016162:Genes, Wilms Tumor; D005819:Genetic Markers; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D016133:Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D009396:Wilms Tumor / Q000235:genetics*
D015820:Cadherins; D005819:Genetic Markers