TY - JOUR
T1 - TCF21 hypermethylation in genetically quiescent clear cell sarcoma of the kidney
AU - Gooskens, Saskia L.
AU - Gadd, Samantha
AU - Guidry Auvil, Jaime M.
AU - Gerhard, Daniela S.
AU - Khan, Javed
AU - Patidar, Rajesh
AU - Meerzaman, Daoud
AU - Chen, Qing Rong
AU - Hsu, Chih Hao
AU - Yan, Chunhua
AU - Nguyen, Cu
AU - Hu, Ying
AU - Mullighan, Charles G.
AU - Ma, Jing
AU - Jennings, Lawrence J.
AU - de Krijger, Ronald R.
AU - van den Heuvel-Eibrink, Marry M.
AU - Smith, Malcolm A.
AU - Ross, Nicole
AU - Gastier-Foster, Julie M.
AU - Perlman, Elizabeth J.
PY - 2015
Y1 - 2015
N2 - Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood tumor whose molecular pathogenesis remains poorly understood. We analyzed a discovery set of 13 CCSKs for changes in chromosome copy number, mutations, rearrangements, global gene expression and global DNA methylation. No recurrent segmental chromosomal copy number changes or somatic variants (single nucleotide or small insertion/deletion) were identified. One tumor with t(10;17)(q22;p13) involving fusion of YHWAE with NUTM2B was identified. Integrated analysis of expression and methylation data identified promoter hypermethylation and low expression of the tumor suppressor gene TCF21 (Pod-1/capsulin/epicardin) in all CCSKs except the case with t(10;17) (q22;p13). TARID, the long noncoding RNA responsible for demethylating TCF21, was virtually undetectable in most CCSKs. TCF21 hypermethylation and decreased TARID expression were validated in an independent set of CCSK tumor samples. The presence of significant hypermethylation of TCF21, a transcription factor known to be active early in renal development, supports the hypothesis that hypermethylation of TCF21and/or decreased TARID expression lies within the pathogenic pathway of most CCSKs. Future studies are needed to functionally verify a tumorigenic role of TCF21 down-regulation and to tie this to the unique gene expression pattern of CCSK.
AB - Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood tumor whose molecular pathogenesis remains poorly understood. We analyzed a discovery set of 13 CCSKs for changes in chromosome copy number, mutations, rearrangements, global gene expression and global DNA methylation. No recurrent segmental chromosomal copy number changes or somatic variants (single nucleotide or small insertion/deletion) were identified. One tumor with t(10;17)(q22;p13) involving fusion of YHWAE with NUTM2B was identified. Integrated analysis of expression and methylation data identified promoter hypermethylation and low expression of the tumor suppressor gene TCF21 (Pod-1/capsulin/epicardin) in all CCSKs except the case with t(10;17) (q22;p13). TARID, the long noncoding RNA responsible for demethylating TCF21, was virtually undetectable in most CCSKs. TCF21 hypermethylation and decreased TARID expression were validated in an independent set of CCSK tumor samples. The presence of significant hypermethylation of TCF21, a transcription factor known to be active early in renal development, supports the hypothesis that hypermethylation of TCF21and/or decreased TARID expression lies within the pathogenic pathway of most CCSKs. Future studies are needed to functionally verify a tumorigenic role of TCF21 down-regulation and to tie this to the unique gene expression pattern of CCSK.
KW - Clear cell sarcoma of the kidney
KW - Methylation
KW - TARID
KW - TCF21
KW - Whole genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=84937947203&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.4682
DO - 10.18632/oncotarget.4682
M3 - Article
AN - SCOPUS:84937947203
SN - 1949-2553
VL - 6
SP - 15828
EP - 15841
JO - Oncotarget
JF - Oncotarget
IS - 18
ER -