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.
%0 Journal Article
%1 Benetkiewicz.2006
%A Benetkiewicz, M.
%A Stahl, T. D. de
%A Gordor, A.
%A Pfeifer, S.
%A Wittmann, S.
%A Gessler, M.
%A Dumanski, J. P.
%D 2006
%J Int J Cancer
%K *Chromosome 22/*genetics Aberrations Acid Child Child;Preschool Chromosome Chromosomes;Human;Pair DNA;Neoplasm/blood/genetics/isolation Deletion Female Genome;Human Genotype Humans Hybridization/*methods Infant Kidney Male Mapping Monosomy Neoplasms/*genetics Nucleic Tumor/*genetics Wilms purification {\&}
%N 3
%P 571--578
%T Identification of limited regions of genetic aberrations in patients affected with Wilms' tumor using a tiling-path chromosome 22 array
%V 119
%X 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.
@article{Benetkiewicz.2006,
abstract = {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.},
added-at = {2013-01-29T13:47:26.000+0100},
author = {Benetkiewicz, M. and Stahl, T. D. de and Gordor, A. and Pfeifer, S. and Wittmann, S. and Gessler, M. and Dumanski, J. P.},
biburl = {https://www.bibsonomy.org/bibtex/2c8d3b4a9bbaceaf21fe3b63563100361/ebch},
interhash = {9317d2b4a4a8c2ce806459e23e960ee1},
intrahash = {c8d3b4a9bbaceaf21fe3b63563100361},
journal = {Int J Cancer},
keywords = {*Chromosome 22/*genetics Aberrations Acid Child Child;Preschool Chromosome Chromosomes;Human;Pair DNA;Neoplasm/blood/genetics/isolation Deletion Female Genome;Human Genotype Humans Hybridization/*methods Infant Kidney Male Mapping Monosomy Neoplasms/*genetics Nucleic Tumor/*genetics Wilms purification {\&}},
number = 3,
pages = {571--578},
timestamp = {2013-01-29T13:47:38.000+0100},
title = {Identification of limited regions of genetic aberrations in patients affected with Wilms' tumor using a tiling-path chromosome 22 array},
volume = 119,
year = 2006
}