Expression of KRT7 and WT1 differentiates precursor lesions of Wilms’ tumours from those of papillary renal cell tumours and mucinous tubular and spindle cell carcinomas

Szponar, Adrianna; Kovács, Gyula

doi:10.1007/s00428-012-1209-z

Cited by 9 publications

(8 citation statements)

References 14 publications

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“…Of interest, MET is also expressed in 22% of nephrogenic rest and 14% of WTs mainly in well-differentiated epithelial cells, whereas blastemal components are negative in both nephrogenic rests and WTs 19 . In spite of this similarity, the precursor lesions for WT and PRCT correspond to distinct stages of cellular differentiation 20 .…”

Section: Resultsmentioning

confidence: 99%

Recalling Cohnheim's Theory: Papillary Renal Cell Tumor as a Model of Tumorigenesis from Impaired Embryonal Differentiation to Malignant Tumors in Adults

et al. 2018

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We have suggested that papillary renal cell tumor (PRCT) of the kidney arises from nephrogenic rest-like lesions. To approve our hypothesis, we worked up 14 kidneys bearing papillary and 14 ones with conventional renal cell carcinoma (CRCC) histologically and found 42 papillary lesions in average per kidney bearing PRCT. PRCTs are characterized by loss of the Y chromosome and trisomy of chromosomes 7 and 17. The MET and HNF1B are localized to chromosome 7q31 and 17q21 and are frequently amplified in PRCT. We have analyzed the expression of the mutant MET in hereditary PRCTs and precursor lesions and found duplication and expression of the mutated allele. Because both genes are involved in early stage of nephron development, we have analyzed the expression of MET and HNF1B by immunohistochemistry in fetal kidneys, precursor lesions and PRCTs. We detected strong expression of MET and HNF1B in distal compartment of S-shaped body of fetal kidneys and in nephrogenic rest-like precursor lesions. Our finding suggests an association between expression of MET and HNF1B in precursor lesions and development of PRCT. We propose a model involving chromosomal clonal evolution and corresponding gene expression for development of PRCTs from embryonic rests due to impaired differentiation. Our model suggests that PRCT have a natural history distinct from that of most common CRCC.

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Section: Resultsmentioning

confidence: 99%

Recalling Cohnheim's Theory: Papillary Renal Cell Tumor as a Model of Tumorigenesis from Impaired Embryonal Differentiation to Malignant Tumors in Adults

et al. 2018

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“…29 additional events involved truncation, occurring in non-NMD genes and included five of the 29 PD signature genes that we previously identified in this same cohort: the B cell development controller LRRC8C, the solute carrier protein SLC6A8, the ATPase ATP11B, the cell division cycle protein CDC20 and TKTL1 [35]. Two genes showed both fold-change and modified AS: the tumorigenic keratin KRT7 [44] and the oncogene MED29 [44]. Functional analysis revealed that the FIRMA-detected genes were highly enriched with alternative splicing.…”

Section: Resultsmentioning

confidence: 99%

Deep brain stimulation modulates nonsense-mediated RNA decay in Parkinson’s patients leukocytes

Soreq¹,

Bergman

Israel

et al. 2013

BMC Genomics

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BackgroundNonsense-Mediated decay (NMD) selectively degrades mRNA transcripts that carry premature stop codons. NMD is often triggered by alternative splicing (AS) modifications introducing such codons. NMD plays an important regulatory role in brain neurons, but the in vivo dynamics of AS and NMD changes in neurological diseases and under treatment were scarcely explored.ResultsHere, we report exon arrays analysis of leukocyte mRNA AS events prior to and following Deep Brain Stimulation (DBS) neurosurgery, which efficiently improves the motor symptoms of Parkinson’s disease (PD), the leading movement disorder, and is increasingly applied to treat other diseases. We also analyzed publicly available exon array dataset of whole blood cells from mixed early and advanced PD patients. Our in-house exon array dataset of leukocyte transcripts was derived from advanced PD patients’ pre- and post-DBS stimulation and matched healthy control volunteers. The mixed cohort exhibited 146 AS changes in 136 transcripts compared to controls, including 9 NMD protein-level assessed events. In comparison, PD patients from our advanced cohort differed from healthy controls by 319 AS events in 280 transcripts, assessed as inducing 27 protein-level NMD events. DBS stimulation induced 254 AS events in 229 genes as compared to the pre-DBS state including 44 NMD inductions. A short, one hour electrical stimulus cessation caused 234 AS changes in 125 genes compared to ON-stimulus state, 22 of these were assessed for NMD. Functional analysis highlighted disease-induced DNA damage and inflammatory control and its reversal under ON and OFF stimulus as well as alternative splicing in all the tested states.ConclusionsThe study findings indicate a potential role for NMD both in PD and following electrical brain stimulation. Furthermore, our current observations entail future implications for developing therapies for PD, and for interfering with the impaired molecular mechanisms that underlie PD and other neurodegenerative and neurological disorders, as well as DBS-treatable conditions in general.

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“…The similarity of morphological variations in precursor lesions and clinically recognised MTSCC strongly suggest that MTSCC develops from such lesions. In 1882 Cohnheim has postulated 1, -4, -6, -9, -13, -14, -15, -18, -22 -1, -6, -8, -11, -14, -15, -22 1 -1,-3,-4,-6,-9,-11,-13,-14,-15,-17,-21,-22 CDC CHR Antonelli et al (19) that "an error and disregulation" in the embryonal Anlage may lead to development of tumours (17). Wilms' tumour (WT) and papillary RCT have already been recognized as a useful model to explore the tumour development from "not differentiated superabundant" embryonal rest cells (18,19).…”

Section: Discussionmentioning

confidence: 99%

“…Now, we add MTSCC to this group of tumours. WT, MTSCC and papillary RCT display morphological variations corresponding to impaired differentiation of blastemal cells, albeit at different time of mesenchyme to epithelium transition affecting different cell lineages (19). The embryonal origin of MTSCC may explain its morphological variations making the diagnosis uncertain in some cases.…”

Section: Discussionmentioning

confidence: 99%

Embryonal Origin of MTSCC of Kidney May Explain its Morphological Heterogeneity: Diagnostic Impact of Genetic Analysis

Banyai

Vastag

Yusenko

et al. 2017

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Expression of KRT7 and WT1 differentiates precursor lesions of Wilms’ tumours from those of papillary renal cell tumours and mucinous tubular and spindle cell carcinomas

Cited by 9 publications

References 14 publications

Recalling Cohnheim's Theory: Papillary Renal Cell Tumor as a Model of Tumorigenesis from Impaired Embryonal Differentiation to Malignant Tumors in Adults

Recalling Cohnheim's Theory: Papillary Renal Cell Tumor as a Model of Tumorigenesis from Impaired Embryonal Differentiation to Malignant Tumors in Adults

Deep brain stimulation modulates nonsense-mediated RNA decay in Parkinson’s patients leukocytes

Embryonal Origin of MTSCC of Kidney May Explain its Morphological Heterogeneity: Diagnostic Impact of Genetic Analysis

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