TY - JOUR
T1 - Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome
AU - Haruta, Masayuki
AU - Arai, Yasuhito
AU - Okita, Hajime
AU - Tanaka, Yukichi
AU - Takimoto, Tetsuya
AU - Sugino, Ryuichi P.
AU - Yamada, Yasuhiro
AU - Kamijo, Takehiko
AU - Oue, Takaharu
AU - Fukuzawa, Masahiro
AU - Koshinaga, Tsugumichi
AU - Kaneko, Yasuhiko
N1 - Funding Information:
This work was supported by Grants-in-Aid for scientific research (nos. 20390452 , 23390405 , and 24791099 ) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (Y.K., H.O., M.H., T.O., T.K., and M.F.); the Japanese Ministry of Health, Labour and Welfare ( 262701201 ) (Y.K., T.O., T.K., and M.F.); and the Japan Agency for Medical Research and Development, AMED ( 16ck0106068h0003 , 16ck0106070h0003 , and 16ck0106130j0203 ) (Y.K., T.O., T.K., and Y.Y.).
Publisher Copyright:
© 2018 The Authors
PY - 2019/1
Y1 - 2019/1
N2 - To identify prognostic factors, array CGH (aCGH) patterns and mutations in WT1 and 9 other genes were analyzed in 128 unilateral Wilms tumors (WTs). Twenty patients had no aCGH aberrations, and 31 had WT1 alterations [silent and WT1 types: relapse-free survival (RFS), 95% and 83%, respectively]. Seventy-seven patients had aCGH changes without WT1 alterations (nonsilent/non-WT1 type) and were subtyped into those with or without +12, 11q− 16q− or HACE1 loss. RFS was better for those with than those without +12 (P =.010) and worse for those with than those without 11q− 16q− or HACE1 loss (P =.001,.025, or 1.2E-04, respectively). Silent and WT1 type and 8 subtype tumors were integrated and classified into 3 risk groups: low risk for the silent type and +12 subgroup; high risk for the no +12 plus 11q− 16q− or HACE1 loss subgroup; intermediate risk for the WT1 type and no +12 plus no 11q− 16q− or HACE1 loss subgroup. Among the 27 WTs examined, the expression of 146 genes on chromosome 12 was stronger in +12 tumors than in no +12 tumors, while that of 10 genes on 16q was weaker in 16q− tumors than in no 16q− tumors. Overexpression in 75 out of 146 upregulated genes and underexpression in 7 out of 10 downregulated genes correlated with better and worse overall survival, respectively, based on the public database. +12 was identified as a potential new marker predicting a favorable outcome, and chromosome abnormalities may be related to altered gene expression associated with these abnormalities.
AB - To identify prognostic factors, array CGH (aCGH) patterns and mutations in WT1 and 9 other genes were analyzed in 128 unilateral Wilms tumors (WTs). Twenty patients had no aCGH aberrations, and 31 had WT1 alterations [silent and WT1 types: relapse-free survival (RFS), 95% and 83%, respectively]. Seventy-seven patients had aCGH changes without WT1 alterations (nonsilent/non-WT1 type) and were subtyped into those with or without +12, 11q− 16q− or HACE1 loss. RFS was better for those with than those without +12 (P =.010) and worse for those with than those without 11q− 16q− or HACE1 loss (P =.001,.025, or 1.2E-04, respectively). Silent and WT1 type and 8 subtype tumors were integrated and classified into 3 risk groups: low risk for the silent type and +12 subgroup; high risk for the no +12 plus 11q− 16q− or HACE1 loss subgroup; intermediate risk for the WT1 type and no +12 plus no 11q− 16q− or HACE1 loss subgroup. Among the 27 WTs examined, the expression of 146 genes on chromosome 12 was stronger in +12 tumors than in no +12 tumors, while that of 10 genes on 16q was weaker in 16q− tumors than in no 16q− tumors. Overexpression in 75 out of 146 upregulated genes and underexpression in 7 out of 10 downregulated genes correlated with better and worse overall survival, respectively, based on the public database. +12 was identified as a potential new marker predicting a favorable outcome, and chromosome abnormalities may be related to altered gene expression associated with these abnormalities.
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U2 - 10.1016/j.neo.2018.10.007
DO - 10.1016/j.neo.2018.10.007
M3 - Article
C2 - 30530054
AN - SCOPUS:85057840322
SN - 1522-8002
VL - 21
SP - 117
EP - 131
JO - Neoplasia (United States)
JF - Neoplasia (United States)
IS - 1
ER -