Abstract
Hepatocyte nuclear factor 1 beta (HNF1B) is a transcription factor which plays a crucial role in nephronogenesis, and its germline mutations have been associated with kidney developmental disorders. However, the effects of HNF1B somatic exonic mutations and its role in the pathogenesis of kidney tumours has not yet been elucidated. Depending on the type of the tumour HNF1B may act as a tumour suppressor or oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using an immunohistochemical approach, and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B in 130 cases of renal tumours (121 renal cell carcinomas, 9 oncocytomas). In the subset of clear cell renal cell carcinoma (ccRCC), decreased HNF1B expression was associated with a higher tumour grade and higher T stage. The mutation analysis revealed no mutations in the analysed samples. Promoter methylation was detected in two ccRCCs and one oncocytoma. The results of our work on a limited sample set suggest that while in papillary renal cell carcinoma HNF1B functions as an oncogene, in ccRCC and chRCC it may act in a tumour suppressive fashion.
Highlights
Hepatocyte nuclear factor 1 beta (HNF1B, previously known as TCF2) is a tissue-specific, developmentally regulated transcription factor which is crucial for the embryonic development of organs derived from ventral endoderm, including the kidneys, pancreas, gastrointestinal system, liver, biliary tract and genital tract[1, 2]
We found that promoter methylation was a rare event, only detected in 3 cases (2 clear cell renal cell carcinoma (ccRCC), 1 renal oncocytoma (RO)), suggesting that there are other mechanisms aside from promoter methylation involved in the regulation of HNF1B expression
RCC is comprised of a diverse spectrum of carcinoma subtypes with distinct morphology, molecular pathology, pathogenesis, and prognosis
Summary
Hepatocyte nuclear factor 1 beta (HNF1B, previously known as TCF2) is a tissue-specific, developmentally regulated transcription factor which is crucial for the embryonic development of organs derived from ventral endoderm, including the kidneys, pancreas, gastrointestinal system, liver, biliary tract and genital tract[1, 2]. More than 100 different germline HNF1B mutations scattered across the gene have been reported in literature, all presenting with a varied range of phenotypes of associated kidney, urogenital tract, and pancreas disorders[8, 12]. They comprise mainly base substitutions, small insertion-deletions, or whole-gene deletions which are inherited in an autosomal dominant fashion, up to 50% of them arise de novo[5, 10, 13]. HNF1B plays such a profound role in the development of the kidneys, knowledge about its involvement in the pathogenesis of kidney tumours is sparse, with only a handful of published studies focusing on the Scientific Reports | (2020) 10:17151
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