E-MTAB-1269 - Transcription profiling by array of human male kidney renal cell adenocarcinoma to investigate the hypoxia responsive pathway

Released on 3 September 2013, last updated on 3 May 2014
Homo sapiens
Samples (16)
Array (1)
Protocols (6)
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.
Experiment types
transcription profiling by array, co-expression, dye swap, individual genetic characteristics, reference
An unexpected VHL germline mutation shed a new light on von Hippel-Lindau disease and Chuvash polycythemia associated mutants.
Investigation descriptionE-MTAB-1269.idf.txt
Sample and data relationshipE-MTAB-1269.sdrf.txt
Raw data (1)E-MTAB-1269.raw.1.zip
Array designA-AGIL-28.adf.txt