Copy number profiling in von hippel-lindau disease renal cell carcinoma

Salwati Shuib, Wenbin Wei, Hariom Sur, Mark R. Morris, Dominic Mcmullan, Eleanor Rattenberry, Esther Meyer, Patrick H. Maxwell, Takeshi Kishida, Masahiro Yao, Farida Latif, Eamonn R. Maher

Research output: Contribution to journalArticle

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Abstract

Germline mutations in the VHL tumor suppressor gene cause von Hippel-Lindau (VHL) disease and somatic VHL mutations occur in the majority of clear cell renal cell carcinoma (cRCC). To compare copy number abnormalities (CNAs) between cRCC from VHL patients and sporadic cRCC cases without detectable somatic VHL mutations, we analyzed 34 cRCC with Affymetrix 250K arrays. To increase the power of the study, we then combined our results with those of a previously published study and compared CNAs in VHL and non-VHL related cRCC using the genomic identification of significant targets in cancer (GISTIC) program. In VHL, cRCC GISTIC analysis identified four statistically significant regions of copy number gain and four statistically significant regions of deletion that occurred in >10% of tumors analyzed. Sporadic cRCC without detectable VHL mutations had, on average, more copy number abnormalities than VHL cRCC though the most common regions of loss/gain (e.g., 3p and 14q loss and 5q gain) were present in both tumor sets. However, CNAs on chromosome arms 7p (gain) and 8p (loss) were only detected in VHL RCC. Although individual copy number abnormality peaks contained clear candidate cancer genes in some cases (e.g., the 3p loss peak in VHL cRCC contained only six genes including VHL), most peaks contained many genes. To date, only a minority of the candidate genes included in these peaks have been analyzed for mutation or epigenetic inactivation in cRCC but TNFRSF10C and DUSP4 map to the 8p region deleted in VHL cRCC and TP53 and HIF2A (EPAS1) mapped to CNA loss and gain peaks (chromosomes 17 and 2, respectively) detected in sporadic VHL wild-type cRCC.

Original languageEnglish
Pages (from-to)479-488
Number of pages10
JournalGenes Chromosomes and Cancer
Volume50
Issue number7
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

Fingerprint

von Hippel-Lindau Disease
Renal Cell Carcinoma
Mutation
Neoplasms
Genes
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 2
Germ-Line Mutation
Neoplasm Genes
Tumor Suppressor Genes
Epigenomics
Chromosome Aberrations

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Shuib, S., Wei, W., Sur, H., Morris, M. R., Mcmullan, D., Rattenberry, E., ... Maher, E. R. (2011). Copy number profiling in von hippel-lindau disease renal cell carcinoma. Genes Chromosomes and Cancer, 50(7), 479-488. https://doi.org/10.1002/gcc.20865

Copy number profiling in von hippel-lindau disease renal cell carcinoma. / Shuib, Salwati; Wei, Wenbin; Sur, Hariom; Morris, Mark R.; Mcmullan, Dominic; Rattenberry, Eleanor; Meyer, Esther; Maxwell, Patrick H.; Kishida, Takeshi; Yao, Masahiro; Latif, Farida; Maher, Eamonn R.

In: Genes Chromosomes and Cancer, Vol. 50, No. 7, 07.2011, p. 479-488.

Research output: Contribution to journalArticle

Shuib, S, Wei, W, Sur, H, Morris, MR, Mcmullan, D, Rattenberry, E, Meyer, E, Maxwell, PH, Kishida, T, Yao, M, Latif, F & Maher, ER 2011, 'Copy number profiling in von hippel-lindau disease renal cell carcinoma', Genes Chromosomes and Cancer, vol. 50, no. 7, pp. 479-488. https://doi.org/10.1002/gcc.20865
Shuib, Salwati ; Wei, Wenbin ; Sur, Hariom ; Morris, Mark R. ; Mcmullan, Dominic ; Rattenberry, Eleanor ; Meyer, Esther ; Maxwell, Patrick H. ; Kishida, Takeshi ; Yao, Masahiro ; Latif, Farida ; Maher, Eamonn R. / Copy number profiling in von hippel-lindau disease renal cell carcinoma. In: Genes Chromosomes and Cancer. 2011 ; Vol. 50, No. 7. pp. 479-488.
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