Transcriptomics

Dataset Information

240

Transcription profiling by array of human male kidney renal cell adenocarcinoma to investigate the hypoxia responsive pathway


ABSTRACT: VHL is a tumor suppressor gene involved in the oxygen-sensing pathway whose germline mutations predispose to distinct phenotypes. Heterozygous mutations predispose to von Hippel-Lindau disease characterized by the development of multiple tumors (including hemangioblastomas, renal cell carcinomas and pheochromocytomas)1-3. More recently, a specific VHL-R200W mutation was shown to be responsible for Chuvash Polycythemia in homozygous carriers whereas heterozygous individuals have no clinical manifestation4. We report here a family carrying, on the same allele, VHL mutations characteristics of the two types of disease (a Chuvash polycythemia-R200W mutation and a von Hippel-Lindau disease-R161Q mutation). Genotyping, modeling analysis and functional studies, including transcriptomic profile of the distinct mutants validated for the first time on direct HIF target genes, show a gradual capacity of the VHL mutants to regulate the hypoxia responsive pathway that correlate with the severity of the developed phenotype. Our study provide original results that illuminate genotype/phenotype correlations in von Hippel-Lindau disease.

ORGANISM(S): Homo sapiens  

SUBMITTER: JUSTINE JG GUEGAN  

PROVIDER: E-MTAB-1269 | ArrayExpress | 2013-09-03

REPOSITORIES: ArrayExpress

altmetric image

Publications


The classic model of tumor suppression implies that malignant transformation requires full "two-hit" inactivation of a tumor-suppressor gene. However, more recent work in mice has led to the proposal of a "continuum" model that involves more fluid concepts such as gene dosage-sensitivity and tissue specificity. Mutations in the tumor-suppressor gene von Hippel-Lindau (VHL) are associated with a complex spectrum of conditions. Homozygotes or compound heterozygotes for the R200W germline mutation  ...[more]

Similar Datasets

2015-09-15 | E-MTAB-3820 | ArrayExpress
2012-03-02 | E-MTAB-1013 | ArrayExpress
2013-02-01 | E-MTAB-966 | ArrayExpress
2015-01-22 | E-GEOD-65168 | ArrayExpress
2013-12-11 | E-MTAB-1132 | ArrayExpress
2013-08-01 | E-MTAB-949 | ArrayExpress
2014-05-01 | E-MTAB-1742 | ArrayExpress
2013-06-30 | E-MTAB-1221 | ArrayExpress
2010-12-31 | E-TABM-873 | ArrayExpress
2013-08-13 | E-MTAB-993 | ArrayExpress