Identification of novel HNF1B mRNA splicing variants and their qualitative and semi-quantitative profile in selected healthy and tumor tissues


Session type:

Jan Hojny1,Nikola Hajkova1,Michaela Bartu1,Pavel Dundr1,Ivana Ticha1
1Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague



Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor crucial for the development of several tissues and a promising biomarker of certain solid tumors. Two HNF1B alternative splicing variants (ASVs) have been described, however, the complete spectrum, prevalence and role of HNF1B ASVs in tumorigenesis are unclear. In light of the unclear and equivocal data presented in literature, our aim was to characterize the spectrum of HNF1B mRNA splicing variants across different tissues.


RNA (RQN>8,8) isolated from RNAlater stored tissues (uterine corpus, ovary, large intestine, kidney, pancreas and prostate carcinomas with selected paired healthy tissues) was subjected to cDNA synthesis by SSIII transcriptase and random hexamers. Four randomly selected samples of respective tissue type were pooled and analyzed using in-house multiplex PCR (mPCR) of all presented exon-exon junctions and NGS (Illumina).


We identified 45 ASVs, of which 43 were novel. The spectrum and relative quantity of expressed ASVs mRNA differed among the analyzed tissue types. Four HNF1B transcripts, including two known (3p, Δ7_8) and two novel (Δ7, Δ8) ASVs with unknown biological functions, were detected in all the analyzed tissues. A comparable portion of all ASVs was identified in most of the analyzed tissues with the exception of an endometrial carcinoma and prostate hyperplasia. In high-grade serous carcinoma only four ASVs were detected, in contrast to the other tissues (15-31 variants).


Our study reveals the complete spectrum of HNF1B ASVs in selected tissues. Characterization of the spectrum of HNF1B ASVs is a necessary prerequisite for further expression studies to delineate the HNF1B splicing pattern and potential ASVs functional impact.

Supported by MZCR projects RVO 64165, and AZV17-28404A.