Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping

Christian Pavlovich, Hesed Padilla-Nash, Danny Wangsa, Michael L. Nickerson, Vera Matrosova, W. Marston Linehan, Thomas Ried, John L. Phillips

Research output: Contribution to journalArticle

Abstract

We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (±2.7) in the primary tumors and 19.3 (±4.6) in the cell lines. Both whole-chromosome and chromosome-segment imbalances were noted by CGH: consistent losses or gains included +5q23→ter (100%), -3p14→ter (80%), and +7 (70%). All VHL mutations and 83% of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole-chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (I 0.7/case), of which the majority were unbalanced translocations.

Original languageEnglish (US)
Pages (from-to)252-260
Number of pages9
JournalGenes Chromosomes and Cancer
Volume37
Issue number3
DOIs
StatePublished - Jul 1 2003

Fingerprint

Spectral Karyotyping
Comparative Genomic Hybridization
Aneuploidy
Renal Cell Carcinoma
Chromosomes
Cell Line
Neoplasms
Kidney
Mutation
Chromosomes, Human, Pair 7
Nephrectomy
Carcinogenesis
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping. / Pavlovich, Christian; Padilla-Nash, Hesed; Wangsa, Danny; Nickerson, Michael L.; Matrosova, Vera; Linehan, W. Marston; Ried, Thomas; Phillips, John L.

In: Genes Chromosomes and Cancer, Vol. 37, No. 3, 01.07.2003, p. 252-260.

Research output: Contribution to journalArticle

Pavlovich, Christian ; Padilla-Nash, Hesed ; Wangsa, Danny ; Nickerson, Michael L. ; Matrosova, Vera ; Linehan, W. Marston ; Ried, Thomas ; Phillips, John L. / Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping. In: Genes Chromosomes and Cancer. 2003 ; Vol. 37, No. 3. pp. 252-260.
@article{b712f299c6ad410e8cd7f8dccc161a64,
title = "Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping",
abstract = "We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (±2.7) in the primary tumors and 19.3 (±4.6) in the cell lines. Both whole-chromosome and chromosome-segment imbalances were noted by CGH: consistent losses or gains included +5q23→ter (100{\%}), -3p14→ter (80{\%}), and +7 (70{\%}). All VHL mutations and 83{\%} of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole-chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (I 0.7/case), of which the majority were unbalanced translocations.",
author = "Christian Pavlovich and Hesed Padilla-Nash and Danny Wangsa and Nickerson, {Michael L.} and Vera Matrosova and Linehan, {W. Marston} and Thomas Ried and Phillips, {John L.}",
year = "2003",
month = "7",
day = "1",
doi = "10.1002/gcc.10209",
language = "English (US)",
volume = "37",
pages = "252--260",
journal = "Genes Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping

AU - Pavlovich, Christian

AU - Padilla-Nash, Hesed

AU - Wangsa, Danny

AU - Nickerson, Michael L.

AU - Matrosova, Vera

AU - Linehan, W. Marston

AU - Ried, Thomas

AU - Phillips, John L.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (±2.7) in the primary tumors and 19.3 (±4.6) in the cell lines. Both whole-chromosome and chromosome-segment imbalances were noted by CGH: consistent losses or gains included +5q23→ter (100%), -3p14→ter (80%), and +7 (70%). All VHL mutations and 83% of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole-chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (I 0.7/case), of which the majority were unbalanced translocations.

AB - We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (±2.7) in the primary tumors and 19.3 (±4.6) in the cell lines. Both whole-chromosome and chromosome-segment imbalances were noted by CGH: consistent losses or gains included +5q23→ter (100%), -3p14→ter (80%), and +7 (70%). All VHL mutations and 83% of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole-chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (I 0.7/case), of which the majority were unbalanced translocations.

UR - http://www.scopus.com/inward/record.url?scp=0038546730&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038546730&partnerID=8YFLogxK

U2 - 10.1002/gcc.10209

DO - 10.1002/gcc.10209

M3 - Article

C2 - 12759923

AN - SCOPUS:0038546730

VL - 37

SP - 252

EP - 260

JO - Genes Chromosomes and Cancer

JF - Genes Chromosomes and Cancer

SN - 1045-2257

IS - 3

ER -