Identification of limited regions of genetic aberrations in patients affected with Wilms' tumor using a tiling-path chromosome 22 array.
Wilms' tumor (WT) is one of the most common solid tumors of childhood. The genetics of this disorder is complex and few studies have suggested allelic loss of chromosome 22 as a frequent aberration. To assess tumor- and possible germline-specific regions affected with gene copy number variations on this chromosome, we applied a high-resolution genomic clone-based chromosome 22 array to a series of 28 WT samples and the paired blood-derived DNA of the patients. The group of tumors was enriched for cases with metastases, relapse or fatal outcome, criteria that were expected to yield a higher number of alterations on chromosome 22. Overall, the array-based form of comparative genomic hybridization (array-CGH) analysis revealed genomic changes in 53% (15 out of 28) of cases. We identified hemizygous deletion of the whole arm of 22q in 3 tumors (11%). Furthermore, a complex amplifier genotype was detected in 8 samples, presenting regions of gain along the chromosome, which defined 7 distinct minimal overlapping segments. The distribution of aberrations in 4 additional cases displaying regional genomic imbalances delimited 2 tumor suppressor/oncogene candidate loci, 1 in the proximal and the other in the terminal part of 22q. Analysis of these regions revealed the presence of several candidate genes that may play a role in the development of WT. These findings demonstrate the power of array-CGH in the determination of DNA copy number alterations and further strength the notion that WT-associated genes exist on this chromosome.
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Magdalena.Benetkiewicz@genpat.uu.se
Magdalena
M
Benetkiewicz
Teresita
T
Díaz de Ståhl
Anita
A
Gördör
Susan
S
Pfeifer
Stefanie
S
Wittmann
Manfred
M
Gessler
Jan P
JP
Dumanski
D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D009006:Monosomy; D009693:Nucleic Acid Hybridization / Q000379:methods*; D009396:Wilms Tumor / Q000235:genetics*
D004273:DNA, Neoplasm