Combined classical cytogenetics and microarray‐based genomic copy number analysis reveal frequent 3;5 rearrangements in clear cell renal cell carcinoma
- 13 April 2010
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 49 (7), 610-619
- https://doi.org/10.1002/gcc.20771
Abstract
Karyotypic analysis and genomic copy number analysis with single nucleotide polymorphism (SNP)‐based microarrays were compared with regard to the detection of recurrent genomic imbalances in 20 clear cell renal cell carcinomas (ccRCCs). Genomic imbalances were identified in 19 of 20 tumors by DNA copy number analysis and in 15 tumors by classical cytogenetics. A statistically significant correlation was observed between the number of genomic imbalances and tumor stage. The most common genomic imbalances were loss of 3p and gain of 5q. Other recurrent genomic imbalances seen in at least 15% of tumors included losses of 1p32.3‐p33, 6q23.1‐qter and 14q and gain of chromosome 7. The SNP‐based arrays revealed losses of 3p in 16 of 20 tumors, with the highest frequency being at 3p21.31‐p22.1 and 3p24.3‐p25.3, the latter encompassing the VHL locus. One other tumor showed uniparental disomy of chromosome 3. Thus, altogether loss of 3p was identified in 17 of 20 (85%) cases. Fourteen tumors showed both overlapping losses of 3p and overlapping gains of 5q, and the karyotypic assessment performed in parallel revealed that these imbalances arose via unbalanced 3;5 translocations. Among the latter, there were common regions of loss at 3p21.3‐pter and gain at 5q34‐qter. These data suggest that DNA copy number analysis will supplant karyotypic analysis of tumor types such as ccRCC that are characterized by recurrent genomic imbalances, rather than balanced rearrangements. These findings also suggest that the 5q duplication/3p deficiency resulting from unbalanced 3;5 translocations conveys a proliferative advantage of particular importance in ccRCC tumorigenesis.Keywords
This publication has 18 references indexed in Scilit:
- Induced Chromosomal Proximity and Gene Fusions in Prostate CancerScience, 2009
- Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the KidneyCancer Research, 2009
- Cytogenetic Profile Predicts Prognosis of Patients With Clear Cell Renal Cell CarcinomaJournal of Clinical Oncology, 2009
- Identification of copy number alterations and its association with pathological features in clear cell and papillary RCCCancer Letters, 2008
- Two novel VHL targets, TGFBI (BIGH3) and its transactivator KLF10, are up-regulated in renal clear cell carcinoma and other tumorsBiochemical and Biophysical Research Communications, 2008
- Genome-wide screening of copy number alterations and LOH events in renal cell carcinomas and integration with gene expression profileMolecular Cancer, 2008
- A Comparison of DNA Copy Number Profiling PlatformsCancer Research, 2007
- High‐resolution analysis of DNA copy number alterations and gene expression in renal clear cell carcinomaThe Journal of Pathology, 2007
- Mutations of the VHL tumour suppressor gene in renal carcinomaNature Genetics, 1994
- Chromosome alterations in 21 non‐small cell lung carcinomasGenes, Chromosomes and Cancer, 1990