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Clin Cancer Res. 2013 Sep 1;19(17):4673-84. doi: 10.1158/1078-0432.CCR-12-3825. Epub 2013 Jul 1.

Genomic heterogeneity of translocation renal cell carcinoma.

Author information

1
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Departments of Pathology & Immunology and Human & Molecular Genetics, Baylor College of Medicine, Houston, Texas.
3
Department of Genetics and INSERM U830, Institut Curie, Paris, France.
4
Department of Pathology, Hôpital Saint Joseph, Paris, France.
5
Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
6
Department of Pathology, Hôpital Foch, Suresnes, France.
7
Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
8
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
9
Department of Pathology, Texas Children's Hospital, Houston, Texas.
10
Department of Pathology, Loyola University Hospital, Chicago, Illinois.
11
Departments of Medicine and Pathology, University of Colorado School of Medicine, Aurora, Colorado.
12
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
13
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
14
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
#
Contributed equally

Abstract

PURPOSE:

Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity.

EXPERIMENTAL DESIGN:

Cytogenomic analysis was conducted with 250K single-nucleotide polymorphism microarrays on 16 tumor specimens and four cell lines. LINE-1 methylation, a surrogate marker of DNA methylation, was conducted on 27 cases using pyrosequencing.

RESULTS:

tRCC showed cytogenomic heterogeneity, with 31.2% and 18.7% of cases presenting similarities with clear-cell and papillary RCC profiles, respectively. The most common alteration was a 17q gain in seven tumors (44%), followed by a 9p loss in six cases (37%). Less frequent were losses of 3p and 17p in five cases (31%) each. Patients with 17q gain were older (P=0.0006), displayed more genetic alterations (P<0.003), and had a worse outcome (P=0.002) than patients without it. Analysis comparing gene-expression profiling of a subset of tumors bearing 17q gain and those without suggest large-scale dosage effects and TP53 haploinsufficiency without any somatic TP53 mutation identified. Cell line-based cytogenetic studies revealed that 17q gain can be related to isochromosome 17 and/or to multiple translocations occurring around 17q breakpoints. Finally, LINE-1 methylation was lower in tRCC tumors from adults compared with tumors from young patients (71.1% vs. 76.7%; P=0.02).

CONCLUSIONS:

Our results reveal genomic heterogeneity of tRCC with similarities to other renal tumor subtypes and raise important questions about the role of TFEB/TFE3 translocations and other chromosomal imbalances in tRCC biology.

PMID:
23817689
PMCID:
PMC3882157
DOI:
10.1158/1078-0432.CCR-12-3825
[Indexed for MEDLINE]
Free PMC Article

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