TY - JOUR
T1 - Noncoding RNA Expression and Targeted Next-Generation Sequencing Distinguish Tubulocystic Renal Cell Carcinoma (TC-RCC) from Other Renal Neoplasms
AU - Lawrie, Charles H.
AU - Armesto, María
AU - Fernandez-Mercado, Marta
AU - Arestín, María
AU - Manterola, Lorea
AU - Goicoechea, Ibai
AU - Larrea, Erika
AU - Caffarel, María M.
AU - Araujo, Angela M.
AU - Sole, Carla
AU - Sperga, Māris
AU - Alvarado-Cabrero, Isabel
AU - Michal, Michal
AU - Hes, Ondrej
AU - López, José I.
N1 - Funding Information:
Supported by the IKERBASQUE Foundation for Science, Ministry of Economy & Competitiveness of Spanish central government, and Fondo Europeo de Desarrollo Regional (FEDER) grants PI12/00663, PIE13/00048, DTS14/00109, and PI15/00275 (C.H.L.); Department of Economic Development & Competitiveness and the Department of Health of Basque government (C.H.L.); Spanish Association Against Cancer (AECC) (C.H.L., M.F.-M., and I.G.); the Provincial Council of Guipuzcoa (DFG) (C.H.L. and M.F.-M.); Instituto de Salud “Carlos III” (ISCIII) grant PI16/00169 (M.F.-M.); IKERBASQUE Foundation for Science (M.M.C.); ISCIII Ministry of Economy & Competitiveness of Spanish central government (M.M.C.); and the Ministry of Economy & Competitiveness of the Spanish central government (E.L.).
Publisher Copyright:
© 2018 American Society for Investigative Pathology and the Association for Molecular Pathology
PY - 2018/1
Y1 - 2018/1
N2 - Tubulocystic renal cell carcinoma (TC-RCC) is a rare recently described renal neoplasm characterized by gross, microscopic, and immunohistochemical differences from other renal tumor types and was recently classified as a distinct entity. However, this distinction remains controversial particularly because some genetic studies suggest a close relationship with papillary RCC (PRCC). The molecular basis of this disease remains largely unexplored. We therefore performed noncoding (nc) RNA/miRNA expression analysis and targeted next-generation sequencing mutational profiling on 13 TC-RCC cases (11 pure, two mixed TC-RCC/PRCC) and compared with other renal neoplasms. The expression profile of miRNAs and other ncRNAs in TC-RCC was distinct and validated 10 differentially expressed miRNAs by quantitative RT-PCR, including miR-155 and miR-34a, that were significantly down-regulated compared with PRCC cases (n = 22). With the use of targeted next-generation sequencing we identified mutations in 14 different genes, most frequently (>60% of TC-RCC cases) in ABL1 and PDFGRA genes. These mutations were present in <5% of clear cell RCC, PRCC, or chromophobe RCC cases (n > 600) of The Cancer Genome Atlas database. In summary, this study is by far the largest molecular study of TC-RCC cases and the first to investigate either ncRNA expression or their genomic profile. These results add molecular evidence that TC-RCC is indeed a distinct entity from PRCC and other renal neoplasms.
AB - Tubulocystic renal cell carcinoma (TC-RCC) is a rare recently described renal neoplasm characterized by gross, microscopic, and immunohistochemical differences from other renal tumor types and was recently classified as a distinct entity. However, this distinction remains controversial particularly because some genetic studies suggest a close relationship with papillary RCC (PRCC). The molecular basis of this disease remains largely unexplored. We therefore performed noncoding (nc) RNA/miRNA expression analysis and targeted next-generation sequencing mutational profiling on 13 TC-RCC cases (11 pure, two mixed TC-RCC/PRCC) and compared with other renal neoplasms. The expression profile of miRNAs and other ncRNAs in TC-RCC was distinct and validated 10 differentially expressed miRNAs by quantitative RT-PCR, including miR-155 and miR-34a, that were significantly down-regulated compared with PRCC cases (n = 22). With the use of targeted next-generation sequencing we identified mutations in 14 different genes, most frequently (>60% of TC-RCC cases) in ABL1 and PDFGRA genes. These mutations were present in <5% of clear cell RCC, PRCC, or chromophobe RCC cases (n > 600) of The Cancer Genome Atlas database. In summary, this study is by far the largest molecular study of TC-RCC cases and the first to investigate either ncRNA expression or their genomic profile. These results add molecular evidence that TC-RCC is indeed a distinct entity from PRCC and other renal neoplasms.
UR - http://www.scopus.com/inward/record.url?scp=85038248453&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/29056573/
U2 - 10.1016/j.jmoldx.2017.09.002
DO - 10.1016/j.jmoldx.2017.09.002
M3 - Article
C2 - 29056573
AN - SCOPUS:85038248453
SN - 1525-1578
VL - 20
SP - 34
EP - 45
JO - Journal of Molecular Diagnostics
JF - Journal of Molecular Diagnostics
IS - 1
ER -