Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors

Amy L. Walz; Ariadne Ooms; Samantha Gadd; Daniela S. Gerhard; Malcolm A. Smith; Jamie M. GuidryAuvil; Daoud Meerzaman; Qing Rong Chen; Chih Hao Hsu; Chunhua Yan; Cu Nguyen; Ying Hu; Reanne Bowlby; Denise Brooks; Yussanne Ma; Andrew J. Mungall; Richard A. Moore; Jacqueline Schein; Marco A. Marra; Vicki Huff; Jeffrey S. Dome; Yueh Yun Chi; Charles G. Mullighan; Jing Ma; David A. Wheeler; Oliver A. Hampton; Nadereh Jafari; Nicole Ross; Julie M. Gastier-Foster; Elizabeth J. Perlman

doi:10.1016/j.ccell.2015.01.003

Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors

Amy L. Walz, Ariadne Ooms, Samantha Gadd, Daniela S. Gerhard, Malcolm A. Smith, Jamie M. GuidryAuvil, Daoud Meerzaman, Qing Rong Chen, Chih Hao Hsu, Chunhua Yan, Cu Nguyen, Ying Hu, Reanne Bowlby, Denise Brooks, Yussanne Ma, Andrew J. Mungall, Richard A. Moore, Jacqueline Schein, Marco A. Marra, Vicki HuffJeffrey S. Dome, Yueh Yun Chi, Charles G. Mullighan, Jing Ma, David A. Wheeler, Oliver A. Hampton, Nadereh Jafari, Nicole Ross, Julie M. Gastier-Foster, Elizabeth J. Perlman

Genetics

Research output: Contribution to journal › Article › peer-review

201 Scopus citations

Abstract

We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/. 2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/. 2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.

Original language	English (US)
Pages (from-to)	286-297
Number of pages	12
Journal	Cancer cell
Volume	27
Issue number	2
DOIs	https://doi.org/10.1016/j.ccell.2015.01.003
State	Published - Feb 9 2015

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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Walz, A. L., Ooms, A., Gadd, S., Gerhard, D. S., Smith, M. A., GuidryAuvil, J. M., Meerzaman, D., Chen, Q. R., Hsu, C. H., Yan, C., Nguyen, C., Hu, Y., Bowlby, R., Brooks, D., Ma, Y., Mungall, A. J., Moore, R. A., Schein, J., Marra, M. A., ... Perlman, E. J. (2015). Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors. Cancer cell, 27(2), 286-297. https://doi.org/10.1016/j.ccell.2015.01.003

Walz, AL, Ooms, A, Gadd, S, Gerhard, DS, Smith, MA, GuidryAuvil, JM, Meerzaman, D, Chen, QR, Hsu, CH, Yan, C, Nguyen, C, Hu, Y, Bowlby, R, Brooks, D, Ma, Y, Mungall, AJ, Moore, RA, Schein, J, Marra, MA, Huff, V, Dome, JS, Chi, YY, Mullighan, CG, Ma, J, Wheeler, DA, Hampton, OA, Jafari, N, Ross, N, Gastier-Foster, JM & Perlman, EJ 2015, 'Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors', Cancer cell, vol. 27, no. 2, pp. 286-297. https://doi.org/10.1016/j.ccell.2015.01.003

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title = "Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors",

abstract = "We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/. 2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/. 2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.",

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doi = "10.1016/j.ccell.2015.01.003",

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AU - Walz, Amy L.

AU - Ooms, Ariadne

AU - Gadd, Samantha

AU - Gerhard, Daniela S.

AU - Smith, Malcolm A.

AU - GuidryAuvil, Jamie M.

AU - Meerzaman, Daoud

AU - Chen, Qing Rong

AU - Hsu, Chih Hao

AU - Yan, Chunhua

AU - Nguyen, Cu

AU - Hu, Ying

AU - Bowlby, Reanne

AU - Brooks, Denise

AU - Ma, Yussanne

AU - Mungall, Andrew J.

AU - Moore, Richard A.

AU - Schein, Jacqueline

AU - Marra, Marco A.

AU - Huff, Vicki

AU - Dome, Jeffrey S.

AU - Chi, Yueh Yun

AU - Mullighan, Charles G.

AU - Ma, Jing

AU - Wheeler, David A.

AU - Hampton, Oliver A.

AU - Jafari, Nadereh

AU - Ross, Nicole

AU - Gastier-Foster, Julie M.

AU - Perlman, Elizabeth J.

PY - 2015/2/9

Y1 - 2015/2/9

N2 - We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/. 2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/. 2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.

AB - We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/. 2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/. 2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.

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Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors

Abstract

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