Combined classical cytogenetics and microarray-based genomic copy number analysis reveal frequent 3;5 rearrangements in clear cell renal cell carcinoma.
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.
Pei
Jianming
J
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Feder
Madelyn M
MM
Al-Saleem
Tahseen
T
Liu
Zemin
Z
Liu
Angen
A
Hudes
Gary R
GR
Uzzo
Robert G
RG
Testa
Joseph R
JR
D001669:Biochemical Phenomena; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D020732:Cytogenetic Analysis; D016678:Genome; D006801:Humans; D046228:Microarray Analysis; D009367:Neoplasm Staging; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
Oncol Rep. 2005 May;13(5):949-56
15809763
Cancer Res. 2007 Nov 1;67(21):10173-80
17968032
Genes Chromosomes Cancer. 1990 Nov;2(4):328-38
2176544
Urol Clin North Am. 2003 Aug;30(3):423-36
12953746
Cancer Res. 2001 Nov 1;61(21):7731-8
11691785
Genes Chromosomes Cancer. 2002 May;34(1):58-68
11921283
Neoplasia. 2008 Jul;10(7):634-42
18592004
Int J Cancer. 1987 Aug 15;40(2):171-8
3610386
Cancer Genet Cytogenet. 2005 Jul 1;160(1):43-8
15949569
Cancer Lett. 2008 Dec 18;272(2):260-7
18682315
J Clin Oncol. 2009 Feb 10;27(5):746-53
19124809
Mol Cancer. 2008 Jan 14;7:6
18194544
Nat Genet. 1994 May;7(1):85-90
7915601
Cancer Res. 2009 Jun 1;69(11):4674-81
19470766
J Pathol. 2007 Dec;213(4):392-401
17922474
Biochem Biophys Res Commun. 2008 Jun 13;370(4):536-40
18359287