TY - JOUR
T1 - Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation
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
Y1 - 2016/5/24
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.
AB - 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.
KW - CDKN2A
KW - Collecting duct carcinoma
KW - Solute carrier family genes
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U2 - 10.18632/oncotarget.9093
DO - 10.18632/oncotarget.9093
M3 - Article
C2 - 27144525
AN - SCOPUS:84971510394
SN - 1949-2553
VL - 7
SP - 29901
EP - 29915
JO - Oncotarget
JF - Oncotarget
IS - 21
ER -