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Description
  • Clear cell tubulopapillary renal cell carcinoma (CCPRCC) is a recently described rare renal malignancy that displays characteristic gross, microscopic and immunohistochemical differences from other renal tumour types. However, CCPRCC remains a very poorly understood entity. We therefore sought to elucidate some of the molecular mechanisms involved in this neoplasm by carrying out targeted next-generation sequencing (NGS) to identify associated mutations, and in addition examined the expression of non-coding (nc) RNAs. We identified multiple somatic mutations in CCPRCC cases, including a recurrent [3/14 cases (21%)] non-synonymous T992I mutation in the MET proto-oncogene, a gene associated with epithelial-to-mesenchymal transition (EMT). Using a microarray approach, we found that the expression of mature (n = 1105) and pre-miRNAs (n = 1105), as well as snoRNA and scaRNAs (n = 2214), in CCPRCC cases differed from that of clear cell renal cell carcinoma (CCRCC) or papillary renal cell carcinoma (PRCC) tumours. Surprisingly, and unlike other renal tumour subtypes, we found that all five members of the miR-200 family were over-expressed in CCPRCC cases. As these miRNAs are intimately involved with EMT, we stained CCPRCC cases for E-cadherin, vimentin and β-catenin and found that the tumour cells of all cases were positive for all three markers, a combination rarely reported in other renal tumours that could have diagnostic implications. Taken together with the mutational analysis, these data suggest that EMT in CCPRCC tumour cells is incomplete or blocked, consistent with the indolent clinical course typical of this malignancy. In summary, as well as describing a novel pathological mechanism in renal carcinomas, this study adds to the mounting evidence that CCPRCC should be formally considered a distinct entity. Microarray data have been deposited in the GEO database [GEO accession number (GSE51554)].
  • Clear cell tubulopapillary renal cell carcinoma (CCPRCC) is a recently described rare renal malignancy that displays characteristic gross, microscopic and immunohistochemical differences from other renal tumour types. However, CCPRCC remains a very poorly understood entity. We therefore sought to elucidate some of the molecular mechanisms involved in this neoplasm by carrying out targeted next-generation sequencing (NGS) to identify associated mutations, and in addition examined the expression of non-coding (nc) RNAs. We identified multiple somatic mutations in CCPRCC cases, including a recurrent [3/14 cases (21%)] non-synonymous T992I mutation in the MET proto-oncogene, a gene associated with epithelial-to-mesenchymal transition (EMT). Using a microarray approach, we found that the expression of mature (n = 1105) and pre-miRNAs (n = 1105), as well as snoRNA and scaRNAs (n = 2214), in CCPRCC cases differed from that of clear cell renal cell carcinoma (CCRCC) or papillary renal cell carcinoma (PRCC) tumours. Surprisingly, and unlike other renal tumour subtypes, we found that all five members of the miR-200 family were over-expressed in CCPRCC cases. As these miRNAs are intimately involved with EMT, we stained CCPRCC cases for E-cadherin, vimentin and β-catenin and found that the tumour cells of all cases were positive for all three markers, a combination rarely reported in other renal tumours that could have diagnostic implications. Taken together with the mutational analysis, these data suggest that EMT in CCPRCC tumour cells is incomplete or blocked, consistent with the indolent clinical course typical of this malignancy. In summary, as well as describing a novel pathological mechanism in renal carcinomas, this study adds to the mounting evidence that CCPRCC should be formally considered a distinct entity. Microarray data have been deposited in the GEO database [GEO accession number (GSE51554)]. (en)
Title
  • Targeted next-generation sequencing and non-coding RNA expression analysis fo clear cell papillary renal cell carcinoma suggests distinct pathological mechanisms from other renal tumour subtypes
  • Targeted next-generation sequencing and non-coding RNA expression analysis fo clear cell papillary renal cell carcinoma suggests distinct pathological mechanisms from other renal tumour subtypes (en)
skos:prefLabel
  • Targeted next-generation sequencing and non-coding RNA expression analysis fo clear cell papillary renal cell carcinoma suggests distinct pathological mechanisms from other renal tumour subtypes
  • Targeted next-generation sequencing and non-coding RNA expression analysis fo clear cell papillary renal cell carcinoma suggests distinct pathological mechanisms from other renal tumour subtypes (en)
skos:notation
  • RIV/00216208:11140/14:10281774!RIV15-MSM-11140___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I
http://linked.open...iv/cisloPeriodika
  • 1
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 49315
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11140/14:10281774
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • clear cell papillary renal cell carcinoma; renal carcinoma; EMT; non-coding RNA; miRNA (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [86EAEFFB79AE]
http://linked.open...i/riv/nazevZdroje
  • Journal of Pathology
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 232
http://linked.open...iv/tvurceVysledku
  • Hes, Ondřej
  • Arestin, María
  • Cáceres, Francisco
  • Fernandez-Mercado, Marta
  • Goicoechea, Ibai
  • Larrea, Erika
  • Larrinaga, Gorka
  • Lawrie, Charles H
  • López, José I
  • Manterola, Lorea
http://linked.open...ain/vavai/riv/wos
  • 000327900800005
issn
  • 0022-3417
number of pages
http://bibframe.org/vocab/doi
  • 10.1002/path.4296
http://localhost/t...ganizacniJednotka
  • 11140
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