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Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation
The genetic landscape and molecular features of collecting duct carcinoma (CDC) of the kidney remain largely unknown. Herein, we performed whole exome sequencing (WES) and transcriptome sequencing (RNASeq) on 7 CDC samples (CDC1 −7). Among the 7 samples, 4 samples with matched non-tumor tissue were...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058651/ https://www.ncbi.nlm.nih.gov/pubmed/27144525 http://dx.doi.org/10.18632/oncotarget.9093 |
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author | Wang, Jianmin Papanicolau-Sengos, Antonios Chintala, Sreenivasulu Wei, Lei Liu, Biao Hu, Qiang Miles, Kiersten Marie Conroy, Jeffrey M. Glenn, Sean T. Costantini, Manuela Magi-Galluzzi, Cristina Signoretti, Sabina Choueiri, Toni Gallucci, Michele Sentinelli, Steno Fazio, Vito M. Poeta, Maria Luana Liu, Song Morrison, Carl Pili, Roberto |
author_facet | Wang, Jianmin Papanicolau-Sengos, Antonios Chintala, Sreenivasulu Wei, Lei Liu, Biao Hu, Qiang Miles, Kiersten Marie Conroy, Jeffrey M. Glenn, Sean T. Costantini, Manuela Magi-Galluzzi, Cristina Signoretti, Sabina Choueiri, Toni Gallucci, Michele Sentinelli, Steno Fazio, Vito M. Poeta, Maria Luana Liu, Song Morrison, Carl Pili, Roberto |
author_sort | Wang, Jianmin |
collection | PubMed |
description | The genetic landscape and molecular features of collecting duct carcinoma (CDC) of the kidney remain largely unknown. Herein, we performed whole exome sequencing (WES) and transcriptome sequencing (RNASeq) on 7 CDC samples (CDC1 −7). Among the 7 samples, 4 samples with matched non-tumor tissue were used for copy number analysis by SNP array data. No recurrent somatic SNVs were observed except for MLL, which was found to be mutated (p.V297I and p.F407C) in 2 samples. We identified somatic SNVs in 14 other cancer census genes including: ATM, CREBBP, PRDM1, CBFB, FBXW7, IKZF1, KDR, KRAS, NACA, NF2, NUP98, SS18, TP53, and ZNF521. SNP array data identified a CDKN2A homozygous deletion in 3 samples and SNV analysis showed a non-sense mutation of the CDKN2A gene with unknown somatic status. To estimate the recurrent rate of CDKN2A abnormalities, we performed FISH screening of additional samples and confirmed the frequent loss (62.5%) of CDKN2A expression. Since cisplatin based therapy is the common treatment option for CDC, we investigated the expression of solute carrier (SLC) family transporters and found 45% alteration. In addition, SLC7A11 (cystine transporter, xCT), a cisplatin resistance associated gene, was found to be overexpressed in 4 out of 5 (80%) cases of CDC tumors tested, as compared to matched non-tumor tissue. In summary, our study provides a comprehensive genomic analysis of CDC and identifies potential pathways suitable for targeted therapies. |
format | Online Article Text |
id | pubmed-5058651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50586512016-10-15 Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation Wang, Jianmin Papanicolau-Sengos, Antonios Chintala, Sreenivasulu Wei, Lei Liu, Biao Hu, Qiang Miles, Kiersten Marie Conroy, Jeffrey M. Glenn, Sean T. Costantini, Manuela Magi-Galluzzi, Cristina Signoretti, Sabina Choueiri, Toni Gallucci, Michele Sentinelli, Steno Fazio, Vito M. Poeta, Maria Luana Liu, Song Morrison, Carl Pili, Roberto Oncotarget Priority Research Paper The genetic landscape and molecular features of collecting duct carcinoma (CDC) of the kidney remain largely unknown. Herein, we performed whole exome sequencing (WES) and transcriptome sequencing (RNASeq) on 7 CDC samples (CDC1 −7). Among the 7 samples, 4 samples with matched non-tumor tissue were used for copy number analysis by SNP array data. No recurrent somatic SNVs were observed except for MLL, which was found to be mutated (p.V297I and p.F407C) in 2 samples. We identified somatic SNVs in 14 other cancer census genes including: ATM, CREBBP, PRDM1, CBFB, FBXW7, IKZF1, KDR, KRAS, NACA, NF2, NUP98, SS18, TP53, and ZNF521. SNP array data identified a CDKN2A homozygous deletion in 3 samples and SNV analysis showed a non-sense mutation of the CDKN2A gene with unknown somatic status. To estimate the recurrent rate of CDKN2A abnormalities, we performed FISH screening of additional samples and confirmed the frequent loss (62.5%) of CDKN2A expression. Since cisplatin based therapy is the common treatment option for CDC, we investigated the expression of solute carrier (SLC) family transporters and found 45% alteration. In addition, SLC7A11 (cystine transporter, xCT), a cisplatin resistance associated gene, was found to be overexpressed in 4 out of 5 (80%) cases of CDC tumors tested, as compared to matched non-tumor tissue. In summary, our study provides a comprehensive genomic analysis of CDC and identifies potential pathways suitable for targeted therapies. Impact Journals LLC 2016-04-28 /pmc/articles/PMC5058651/ /pubmed/27144525 http://dx.doi.org/10.18632/oncotarget.9093 Text en Copyright: © 2016 Wang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Priority Research Paper Wang, Jianmin Papanicolau-Sengos, Antonios Chintala, Sreenivasulu Wei, Lei Liu, Biao Hu, Qiang Miles, Kiersten Marie Conroy, Jeffrey M. Glenn, Sean T. Costantini, Manuela Magi-Galluzzi, Cristina Signoretti, Sabina Choueiri, Toni Gallucci, Michele Sentinelli, Steno Fazio, Vito M. Poeta, Maria Luana Liu, Song Morrison, Carl Pili, Roberto Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation |
title | Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation |
title_full | Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation |
title_fullStr | Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation |
title_full_unstemmed | Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation |
title_short | Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation |
title_sort | collecting duct carcinoma of the kidney is associated with cdkn2a deletion and slc family gene up-regulation |
topic | Priority Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058651/ https://www.ncbi.nlm.nih.gov/pubmed/27144525 http://dx.doi.org/10.18632/oncotarget.9093 |
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