which cancer arises after loss of both alleles of a re- 
cessive tumor gene. Since children with Wilms' 
tumor, aniridia, genitourinary malformations, and 
retardation (WAGR syndrome) show overlapping 
deletions involving llpl3, it had been assumed 
that the smallest region of overlap of allelic losses 
in sporadic tumors would be llpl3. However, that 
assumption had not been tested directly. Careful 
mitotic mapping of chromosome 11 on 21 sporadic 
Wilms' tumors was performed, using 10 polymor- 
phic markers for lip. In five of seven tumors with 
allelic loss on lip, the loss was limited to the re- 
gion distal to the WAGR region. The common re- 
gion of overlap of allelic losses was distal to the 7- 
globin gene on lip 15. 5, 50 cM from the previously 
predicted region. Although these data do not ex- 
clude the existence of a Wilms' gene on llpl3, 
they raise the possibility of a second locus on 
llpl5. 
Based on this observation, genetic linkage analy- 
sis was performed, using probes from llpl3 and 
llpl5, on two families with Beckwith-Wiedemann 
syndrome (BWS), a dominantly inherited disorder 
that predisposes to Wilms' and other embryonal tu- 
PUBLICATIONS 
mors. BWS was linked to the insulin gene, on 
lip 15. 5, with an overall maximum lod score of 
3.60 ^ = 0.00). The existence of a dominantly 
transmitted cancer predisposition gene on llpl5 
and loss of heterozygosity for the same region in 
sporadic tumors provide strong evidence for a can- 
didate-recessive tumor gene on llpl5. The labora- 
tory has recently identified two bladder carcinomas 
with allelic loss also limited to llpl5. Thus loss of 
heterozygosity on lip may reflect a generalized 
tumor progression gene at llpl5. Such a role 
would not necessarily contradict a role in tumor 
initiation as well, since the retinoblastoma gene, for 
example, may also be involved in some lung and 
breast cancers. The laboratory is attempting to lo- 
calize and isolate the BWS gene, which may play a 
role in abnormal prenatal growth, predisposition to 
cancer, and tumor progression in common malig- 
nancies. 
Dr. Feinberg is also Associate Professor in the Di- 
vision of Medical Genetics, Department of Internal 
Medicine, and Assistant Professor of Human Genet- 
ics at the University of Michigan Medical School. 
Books and Chapters of Books 
Feinberg, A.P 1989- The molecular genetics of DNA methylation in colorectal cancer. In Cell and Molecular 
Biology of Human Colon Cancer (Augenlicht, L., Ed.). Boca Raton, FL: CRC, pp 187-198. 
Feinberg, A.P, Law, D.J., Lefrangois, D., Delattre, O., and Thomas, G. 1989. A multistep genetic model of 
human colorectal carcinogenesis. In Cancer Cells. Cold Spring Harbor, NY: Cold Spring Harbor, vol 7, pp 
245-248. 
Articles 
Delattre, P, Olschwang, S., Law, D.J., Melot, T, Remvikos, Y, Salmon, R.J., Sastre, X., Validire, R, Feinberg, A.P , 
and Thomas, G. 1989. Multiple genetic alterations in distal and proximal colorectal cancer. Lancet 2:353- 
356. 
Law, D.J., Olschwang, S., Monpezat, J.-P, Lefrangois, D., Jagelman, D., Petrelli, N., Thomas, G., and Feinberg, 
A.P 1988. Concerted nonsyntenic allelic loss in human colorectal carcinoma. Science 241:961-965. 
Ping, A.J., Reeve, A.E., Law, D.J., Young, M.R., Boehnke, M., and Feinberg, A.P 1989. Genetic linkage of 
Beckwith-Wiedemann syndrome to llpl5. Am J Hum Genet 44:720-723. 
Rainier, S., and Feinberg, A.P 1988. Capture and characterization of 5-aza-2'-deoxycytidine-treated 
C3H/10T1/2 cells prior to transformation. Proc Natl Acad Sci C/5A 85:6384-6388. 
Reeve, A.E., Sih, S.A., Raizis, A.M., and Feinberg, A.P 1989- Loss of allelic heterozygosity at a second locus on 
chromosome 11 in sporadic Wilms' tumor cells. Mol Cell Biol 9:1799-1803- 
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