Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: A report from the National Wilms Tumor Study Group

Paul E. Grundy, Norman E. Breslow, Sierra Li, Elizabeth Penman, J. Bruce Beckwith, Michael L. Ritchey, Robert C. Shamberger, Gerald M. Haase, Giulio J. D'Angio, Milton Donaldson, Max J. Coppes, Marcio Malogolowkin, Patricia Shearer, Patrick R.M. Thomas, Roger Macklis, Gail Tomlinson, Vicki Huff, Daniel M. Green

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Abstract

Purpose: To determine if tumor-specific loss of heterozygosity (LOH) for chromosomes 1p or 16q is associated with a poorer prognosis for children with favorable-histology (FH) Wilms tumor entered on the fifth National Wilms Tumor Study (NWTS-5). Patients and Methods: Between August 1995 and June 2002, 2,021 previously untreated children with FH or anaplastic Wilms tumor, clear-cell sarcoma of the kidney (CCSK) or malignant rhabdoid tumor of the kidney (RTK), were treated with stage- and histology-specific therapy. Their tumors were assayed for LOH for polymorphic DNA markers on chromosomes 1p and 16q. Results: LOH for 1p or 16q was rarely observed in CCSK (n = 90) or RTK (n = 22). The relative risk (RR) of relapse for patients with FH stage I to IV tumors with LOH, stratified by stage, was 1.56 for LOH 1p (P = .01) and 1.49 for LOH 16q (P = .01), whereas the RR of death was 1.84 (P = .03) and 1.44 (P = .15), respectively. When the effects of LOH for both regions were considered jointly among patients with stage I to II FH disease, the risks of relapse and death were increased for LOH 1p only (RR = 2.2, P = .02 for relapse; RR = 4.0, P = .02 for death), for LOH 16q only (RR = 1.9, P = .01 and RR = 1.4, P = .60) and for LOH for both regions (RR = 2.9, P = .001 and RR = 4.3, P = .01) in comparison with patients with LOH at neither locus. The risks of relapse and death for patients with stage III to IV FH tumors were increased only with LOH for both regions (RR = 2.4, P = .01 and RR = 2.7, P = .04). Conclusion: Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.

Original languageEnglish (US)
Pages (from-to)7312-7321
Number of pages10
JournalJournal of Clinical Oncology
Volume23
Issue number29
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

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Wilms Tumor
Loss of Heterozygosity
Histology
Chromosomes
Recurrence
Clear Cell Sarcoma
Rhabdoid Tumor
Kidney
Neoplasms
Treatment Failure
Genetic Markers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor : A report from the National Wilms Tumor Study Group. / Grundy, Paul E.; Breslow, Norman E.; Li, Sierra; Penman, Elizabeth; Beckwith, J. Bruce; Ritchey, Michael L.; Shamberger, Robert C.; Haase, Gerald M.; D'Angio, Giulio J.; Donaldson, Milton; Coppes, Max J.; Malogolowkin, Marcio; Shearer, Patricia; Thomas, Patrick R.M.; Macklis, Roger; Tomlinson, Gail; Huff, Vicki; Green, Daniel M.

In: Journal of Clinical Oncology, Vol. 23, No. 29, 01.12.2005, p. 7312-7321.

Research output: Contribution to journalArticle

Grundy, PE, Breslow, NE, Li, S, Penman, E, Beckwith, JB, Ritchey, ML, Shamberger, RC, Haase, GM, D'Angio, GJ, Donaldson, M, Coppes, MJ, Malogolowkin, M, Shearer, P, Thomas, PRM, Macklis, R, Tomlinson, G, Huff, V & Green, DM 2005, 'Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: A report from the National Wilms Tumor Study Group', Journal of Clinical Oncology, vol. 23, no. 29, pp. 7312-7321. https://doi.org/10.1200/JCO.2005.01.2799
Grundy, Paul E. ; Breslow, Norman E. ; Li, Sierra ; Penman, Elizabeth ; Beckwith, J. Bruce ; Ritchey, Michael L. ; Shamberger, Robert C. ; Haase, Gerald M. ; D'Angio, Giulio J. ; Donaldson, Milton ; Coppes, Max J. ; Malogolowkin, Marcio ; Shearer, Patricia ; Thomas, Patrick R.M. ; Macklis, Roger ; Tomlinson, Gail ; Huff, Vicki ; Green, Daniel M. / Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor : A report from the National Wilms Tumor Study Group. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 29. pp. 7312-7321.
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title = "Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: A report from the National Wilms Tumor Study Group",
abstract = "Purpose: To determine if tumor-specific loss of heterozygosity (LOH) for chromosomes 1p or 16q is associated with a poorer prognosis for children with favorable-histology (FH) Wilms tumor entered on the fifth National Wilms Tumor Study (NWTS-5). Patients and Methods: Between August 1995 and June 2002, 2,021 previously untreated children with FH or anaplastic Wilms tumor, clear-cell sarcoma of the kidney (CCSK) or malignant rhabdoid tumor of the kidney (RTK), were treated with stage- and histology-specific therapy. Their tumors were assayed for LOH for polymorphic DNA markers on chromosomes 1p and 16q. Results: LOH for 1p or 16q was rarely observed in CCSK (n = 90) or RTK (n = 22). The relative risk (RR) of relapse for patients with FH stage I to IV tumors with LOH, stratified by stage, was 1.56 for LOH 1p (P = .01) and 1.49 for LOH 16q (P = .01), whereas the RR of death was 1.84 (P = .03) and 1.44 (P = .15), respectively. When the effects of LOH for both regions were considered jointly among patients with stage I to II FH disease, the risks of relapse and death were increased for LOH 1p only (RR = 2.2, P = .02 for relapse; RR = 4.0, P = .02 for death), for LOH 16q only (RR = 1.9, P = .01 and RR = 1.4, P = .60) and for LOH for both regions (RR = 2.9, P = .001 and RR = 4.3, P = .01) in comparison with patients with LOH at neither locus. The risks of relapse and death for patients with stage III to IV FH tumors were increased only with LOH for both regions (RR = 2.4, P = .01 and RR = 2.7, P = .04). Conclusion: Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.",
author = "Grundy, {Paul E.} and Breslow, {Norman E.} and Sierra Li and Elizabeth Penman and Beckwith, {J. Bruce} and Ritchey, {Michael L.} and Shamberger, {Robert C.} and Haase, {Gerald M.} and D'Angio, {Giulio J.} and Milton Donaldson and Coppes, {Max J.} and Marcio Malogolowkin and Patricia Shearer and Thomas, {Patrick R.M.} and Roger Macklis and Gail Tomlinson and Vicki Huff and Green, {Daniel M.}",
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language = "English (US)",
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TY - JOUR

T1 - Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor

T2 - A report from the National Wilms Tumor Study Group

AU - Grundy, Paul E.

AU - Breslow, Norman E.

AU - Li, Sierra

AU - Penman, Elizabeth

AU - Beckwith, J. Bruce

AU - Ritchey, Michael L.

AU - Shamberger, Robert C.

AU - Haase, Gerald M.

AU - D'Angio, Giulio J.

AU - Donaldson, Milton

AU - Coppes, Max J.

AU - Malogolowkin, Marcio

AU - Shearer, Patricia

AU - Thomas, Patrick R.M.

AU - Macklis, Roger

AU - Tomlinson, Gail

AU - Huff, Vicki

AU - Green, Daniel M.

PY - 2005/12/1

Y1 - 2005/12/1

N2 - Purpose: To determine if tumor-specific loss of heterozygosity (LOH) for chromosomes 1p or 16q is associated with a poorer prognosis for children with favorable-histology (FH) Wilms tumor entered on the fifth National Wilms Tumor Study (NWTS-5). Patients and Methods: Between August 1995 and June 2002, 2,021 previously untreated children with FH or anaplastic Wilms tumor, clear-cell sarcoma of the kidney (CCSK) or malignant rhabdoid tumor of the kidney (RTK), were treated with stage- and histology-specific therapy. Their tumors were assayed for LOH for polymorphic DNA markers on chromosomes 1p and 16q. Results: LOH for 1p or 16q was rarely observed in CCSK (n = 90) or RTK (n = 22). The relative risk (RR) of relapse for patients with FH stage I to IV tumors with LOH, stratified by stage, was 1.56 for LOH 1p (P = .01) and 1.49 for LOH 16q (P = .01), whereas the RR of death was 1.84 (P = .03) and 1.44 (P = .15), respectively. When the effects of LOH for both regions were considered jointly among patients with stage I to II FH disease, the risks of relapse and death were increased for LOH 1p only (RR = 2.2, P = .02 for relapse; RR = 4.0, P = .02 for death), for LOH 16q only (RR = 1.9, P = .01 and RR = 1.4, P = .60) and for LOH for both regions (RR = 2.9, P = .001 and RR = 4.3, P = .01) in comparison with patients with LOH at neither locus. The risks of relapse and death for patients with stage III to IV FH tumors were increased only with LOH for both regions (RR = 2.4, P = .01 and RR = 2.7, P = .04). Conclusion: Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.

AB - Purpose: To determine if tumor-specific loss of heterozygosity (LOH) for chromosomes 1p or 16q is associated with a poorer prognosis for children with favorable-histology (FH) Wilms tumor entered on the fifth National Wilms Tumor Study (NWTS-5). Patients and Methods: Between August 1995 and June 2002, 2,021 previously untreated children with FH or anaplastic Wilms tumor, clear-cell sarcoma of the kidney (CCSK) or malignant rhabdoid tumor of the kidney (RTK), were treated with stage- and histology-specific therapy. Their tumors were assayed for LOH for polymorphic DNA markers on chromosomes 1p and 16q. Results: LOH for 1p or 16q was rarely observed in CCSK (n = 90) or RTK (n = 22). The relative risk (RR) of relapse for patients with FH stage I to IV tumors with LOH, stratified by stage, was 1.56 for LOH 1p (P = .01) and 1.49 for LOH 16q (P = .01), whereas the RR of death was 1.84 (P = .03) and 1.44 (P = .15), respectively. When the effects of LOH for both regions were considered jointly among patients with stage I to II FH disease, the risks of relapse and death were increased for LOH 1p only (RR = 2.2, P = .02 for relapse; RR = 4.0, P = .02 for death), for LOH 16q only (RR = 1.9, P = .01 and RR = 1.4, P = .60) and for LOH for both regions (RR = 2.9, P = .001 and RR = 4.3, P = .01) in comparison with patients with LOH at neither locus. The risks of relapse and death for patients with stage III to IV FH tumors were increased only with LOH for both regions (RR = 2.4, P = .01 and RR = 2.7, P = .04). Conclusion: Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.

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