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^*

^*Corresponding author for this work

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

227 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

Funding

The TARGET initiative is supported by NCI Grant U10 CA98543. Work performed under contracts from the NCI, National Institutes of Health (NIH), within HHSN261200800001E includes specimen processing (the COG Biopathology Center), WGS (CGI), WXS (Baylor College of Medicine), miRNA-seq, RNA sequencing, and target capture sequencing (British Columbia Cancer Agency Genome Sciences Center). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the USA government. We thank Patee Gesuwan and Leandro Hermida and the Data Coordinating Center for their support. We also thank the Clinical Applications of Core Technology Laboratory of the Hartwell Center for Bioinformatics and Biotechnology of St. Jude Children’s Research Hospital for performing the copy number analysis and the Northwestern University Genomic Core facility for performing the methylation analysis. This work is also supported by NCI T32 CA079447 (A.L.W.), NIH U10CA42326 (E.J.P.), U10CA98543 (J.S.D., E.J.P.), U24 CA114766, UO1CA88131 (E.J.P.), and the American and Lebanese Syrian Associated Charities of St. Jude (J.M., C.G.M.). We are grateful for the expertise of Karen Novik and Laura Monovich, Patricia Beezhold, Donna Kersey, Debbie-Payne Turner, Mary McNulty, and Yvonne Moyer. This work would not be possible without the dedication of all the experts within the many clinical disciplines at the local institutions and centrally within the COG and the National Wilms Tumor Study Group.

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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10.1016/j.ccell.2015.01.003

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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

@article{f7731f9e168e4e01b6b0c4b2d8d9e5b8,

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.",

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

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

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day = "9",

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

language = "English (US)",

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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

TY - JOUR

T1 - Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors

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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SN - 1535-6108

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JO - Cancer cell

JF - Cancer cell

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ER -

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

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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