Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation

Jianmin Wang, Antonios Papanicolau-Sengos, Sreenivasulu Chintala, Lei Wei, Biao Liu, Qiang Hu, Kiersten Marie Miles, Jeffrey M. Conroy, Sean T. Glenn, Manuela Costantini, Cristina Magi-Galluzzi, Sabina Signoretti, Toni Choueiri, Michele Gallucci, Steno Sentinelli, Vito M. Fazio, Maria Luana Poeta, Song Liu, Carl Morrison, Roberto Pili

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)29901-29915
Number of pages15
JournalOncotarget
Volume7
Issue number21
DOIs
StatePublished - May 24 2016

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Renal Cell Carcinoma
Up-Regulation
Genes
Cisplatin
Single Nucleotide Polymorphism
p16 Genes
Exome
Cystine
Neoplasm Genes
Censuses
Transcriptome
Molecular Biology
Mutation
Therapeutics
Neoplasms

Keywords

  • CDKN2A
  • Collecting duct carcinoma
  • Solute carrier family genes

ASJC Scopus subject areas

  • Oncology

Cite this

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.

In: Oncotarget, Vol. 7, No. 21, 24.05.2016, p. 29901-29915.

Research output: Contribution to journalArticle

Wang, J, Papanicolau-Sengos, A, Chintala, S, Wei, L, Liu, B, Hu, Q, Miles, KM, Conroy, JM, Glenn, ST, Costantini, M, Magi-Galluzzi, C, Signoretti, S, Choueiri, T, Gallucci, M, Sentinelli, S, Fazio, VM, Poeta, ML, Liu, S, Morrison, C & Pili, R 2016, 'Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation', Oncotarget, vol. 7, no. 21, pp. 29901-29915. https://doi.org/10.18632/oncotarget.9093
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. In: Oncotarget. 2016 ; Vol. 7, No. 21. pp. 29901-29915.
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abstract = "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.",
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AU - Wang, Jianmin

AU - Papanicolau-Sengos, Antonios

AU - Chintala, Sreenivasulu

AU - Wei, Lei

AU - Liu, Biao

AU - Hu, Qiang

AU - Miles, Kiersten Marie

AU - Conroy, Jeffrey M.

AU - Glenn, Sean T.

AU - Costantini, Manuela

AU - Magi-Galluzzi, Cristina

AU - Signoretti, Sabina

AU - Choueiri, Toni

AU - Gallucci, Michele

AU - Sentinelli, Steno

AU - Fazio, Vito M.

AU - Poeta, Maria Luana

AU - Liu, Song

AU - Morrison, Carl

AU - Pili, Roberto

PY - 2016/5/24

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N2 - 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.

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