Genomic profiling of papillary renal cell tumours identifies small regions of DNA alterations: a possible role of HNF1B in tumour development

Adrianna Szponar (1) , Maria V Yusenko (1) , Roland Kuiper (2) , Ad Geurts van Kessel (1) , Gyula Kovacs (3)

1 Laboratory of Molecular Oncology
2 Human Genetics
3 Laboratory of Molecular Oncology

Aims: Papillary renal cell tumours (RCT) are characterized by specific trisomies. The aim of this study was to identify small regions of duplications marking putative tumour genes. Methods and results: Full-tiling path BAC array hybridisation of 20 papillary RCTs confirmed the duplication of chromosome 7 and 17 and also displayed smaller regions of gains/amplifications of 1.3 to 13.1 Mb in size. Detailed analysis showed a microamplification of BAC clones containing the MET at the 7q31.2 and also amplification of a DNA segment harbouring the transcription factor HNF1B at chromosome 17q12. Nuclear expression of HNF1B protein was detected in 38 of 67 papillary RCTs, in 5 of 5 mucinous tubular and spindle cell carcinomas (MTSCC) and 5 of 5 metanephric adenomas by immunohistochemistry. Moreover, all the 9 nephrogenic rests containing tubular differentiated structures and all 14 and 5 precursor lesions associated with papillary RCTs and MTSCCs, respectively, showed a strong nuclear positivity when compared to the expressions level in proximal tubuli of the corresponding normal kidney. Conclusions: Our finding indicates a role of HNF1B in association with the high frequency of chromosome 17q duplication in the development of papillary RCTs and MTSCCs as well as in their precursor lesions.

Mots clés: Medicine

Adrianna Szponar, Maria V Yusenko, Roland Kuiper, Ad Geurts van Kessel, Gyula Kovacs. Genomic profiling of papillary renal cell tumours identifies small regions of DNA alterations: a possible role of HNF1B in tumour development. Histopathology, 2011, 58 (6), pp.934. ⟨10.1111/j.1365-2559.2011.03795.x⟩. ⟨hal-00626290⟩