WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk Wilms tumors treated with surgery alone: A children's oncology group study

Elizabeth J. Perlman, Paul E. Grundy, James R. Anderson, Lawrence J. Jennings, Daniel M. Green, Jeffrey S. Dome, Robert C. Shamberger, E. Cristy Ruteshouser, Vicki Huff

Research output: Contribution to journalArticle

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Abstract

Purpose: Children's Oncology Group defines very low-risk Wilms tumors (VLRWT) as stage I favorable histology Wilms tumors weighing less than 550 g in children younger than 24 months of age. VLRWTs may be treated with nephrectomy alone. However, 10% to 15% of VLRWTs relapse without chemotherapy. Previous studies suggest that VLRWTs with low WT1 expression and/or 11p15 loss of heterozygosity (LOH) may have increased risk of relapse. The current study validates these findings within prospectively identified children with VLRWT who did not receive adjuvant chemotherapy. Patients and Methods: Fifty-six VLRWTs (10 relapses) were analyzed for mutation of WT1, CTNNB1, and WTX; for 11p15 LOH using microsatellite analysis; and for H19DMR and KvDMR1 methylation. Results: 11p15 LOH was identified in 19 (41%) of 46 evaluable VLRWTs and was significantly associated with relapse (P < .001); 16 of 19 were isodisomic for 11p15. WT1 mutation was identified in nine (20%) of 45 evaluable VLRWTs and was significantly associated with relapse (P = .004); all nine cases also had 11p15 LOH. All evaluable tumors showing LOH by microsatellite analysis also showed LOH by methylation analysis. Retention of the normal imprinting pattern was identified in 24 of 42 evaluable tumors, and none relapsed. Loss of imprinting at 11p15 was identified in one of 42 tumors. Conclusion: WT1 mutation and 11p15 LOH are associated with relapse in patients with VLRWTs who do not receive chemotherapy. These may provide meaningful biomarkers to stratify patients for reduced chemotherapy in the future. VLRWTs show a different incidence of WT1 mutation and 11p15 imprinting patterns than has been reported in Wilms tumors of all ages.

Original languageEnglish (US)
Pages (from-to)698-703
Number of pages6
JournalJournal of Clinical Oncology
Volume29
Issue number6
DOIs
StatePublished - Feb 20 2011

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Wilms Tumor
Loss of Heterozygosity
Recurrence
Mutation
Drug Therapy
Microsatellite Repeats
Methylation
Neoplasms
Adjuvant Chemotherapy
Nephrectomy
Histology
Biomarkers
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Perlman, Elizabeth J. ; Grundy, Paul E. ; Anderson, James R. ; Jennings, Lawrence J. ; Green, Daniel M. ; Dome, Jeffrey S. ; Shamberger, Robert C. ; Ruteshouser, E. Cristy ; Huff, Vicki. / WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk Wilms tumors treated with surgery alone : A children's oncology group study. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 6. pp. 698-703.
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title = "WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk Wilms tumors treated with surgery alone: A children's oncology group study",
abstract = "Purpose: Children's Oncology Group defines very low-risk Wilms tumors (VLRWT) as stage I favorable histology Wilms tumors weighing less than 550 g in children younger than 24 months of age. VLRWTs may be treated with nephrectomy alone. However, 10{\%} to 15{\%} of VLRWTs relapse without chemotherapy. Previous studies suggest that VLRWTs with low WT1 expression and/or 11p15 loss of heterozygosity (LOH) may have increased risk of relapse. The current study validates these findings within prospectively identified children with VLRWT who did not receive adjuvant chemotherapy. Patients and Methods: Fifty-six VLRWTs (10 relapses) were analyzed for mutation of WT1, CTNNB1, and WTX; for 11p15 LOH using microsatellite analysis; and for H19DMR and KvDMR1 methylation. Results: 11p15 LOH was identified in 19 (41{\%}) of 46 evaluable VLRWTs and was significantly associated with relapse (P < .001); 16 of 19 were isodisomic for 11p15. WT1 mutation was identified in nine (20{\%}) of 45 evaluable VLRWTs and was significantly associated with relapse (P = .004); all nine cases also had 11p15 LOH. All evaluable tumors showing LOH by microsatellite analysis also showed LOH by methylation analysis. Retention of the normal imprinting pattern was identified in 24 of 42 evaluable tumors, and none relapsed. Loss of imprinting at 11p15 was identified in one of 42 tumors. Conclusion: WT1 mutation and 11p15 LOH are associated with relapse in patients with VLRWTs who do not receive chemotherapy. These may provide meaningful biomarkers to stratify patients for reduced chemotherapy in the future. VLRWTs show a different incidence of WT1 mutation and 11p15 imprinting patterns than has been reported in Wilms tumors of all ages.",
author = "Perlman, {Elizabeth J.} and Grundy, {Paul E.} and Anderson, {James R.} and Jennings, {Lawrence J.} and Green, {Daniel M.} and Dome, {Jeffrey S.} and Shamberger, {Robert C.} and Ruteshouser, {E. Cristy} and Vicki Huff",
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WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk Wilms tumors treated with surgery alone : A children's oncology group study. / Perlman, Elizabeth J.; Grundy, Paul E.; Anderson, James R.; Jennings, Lawrence J.; Green, Daniel M.; Dome, Jeffrey S.; Shamberger, Robert C.; Ruteshouser, E. Cristy; Huff, Vicki.

In: Journal of Clinical Oncology, Vol. 29, No. 6, 20.02.2011, p. 698-703.

Research output: Contribution to journalArticle

TY - JOUR

T1 - WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk Wilms tumors treated with surgery alone

T2 - A children's oncology group study

AU - Perlman, Elizabeth J.

AU - Grundy, Paul E.

AU - Anderson, James R.

AU - Jennings, Lawrence J.

AU - Green, Daniel M.

AU - Dome, Jeffrey S.

AU - Shamberger, Robert C.

AU - Ruteshouser, E. Cristy

AU - Huff, Vicki

PY - 2011/2/20

Y1 - 2011/2/20

N2 - Purpose: Children's Oncology Group defines very low-risk Wilms tumors (VLRWT) as stage I favorable histology Wilms tumors weighing less than 550 g in children younger than 24 months of age. VLRWTs may be treated with nephrectomy alone. However, 10% to 15% of VLRWTs relapse without chemotherapy. Previous studies suggest that VLRWTs with low WT1 expression and/or 11p15 loss of heterozygosity (LOH) may have increased risk of relapse. The current study validates these findings within prospectively identified children with VLRWT who did not receive adjuvant chemotherapy. Patients and Methods: Fifty-six VLRWTs (10 relapses) were analyzed for mutation of WT1, CTNNB1, and WTX; for 11p15 LOH using microsatellite analysis; and for H19DMR and KvDMR1 methylation. Results: 11p15 LOH was identified in 19 (41%) of 46 evaluable VLRWTs and was significantly associated with relapse (P < .001); 16 of 19 were isodisomic for 11p15. WT1 mutation was identified in nine (20%) of 45 evaluable VLRWTs and was significantly associated with relapse (P = .004); all nine cases also had 11p15 LOH. All evaluable tumors showing LOH by microsatellite analysis also showed LOH by methylation analysis. Retention of the normal imprinting pattern was identified in 24 of 42 evaluable tumors, and none relapsed. Loss of imprinting at 11p15 was identified in one of 42 tumors. Conclusion: WT1 mutation and 11p15 LOH are associated with relapse in patients with VLRWTs who do not receive chemotherapy. These may provide meaningful biomarkers to stratify patients for reduced chemotherapy in the future. VLRWTs show a different incidence of WT1 mutation and 11p15 imprinting patterns than has been reported in Wilms tumors of all ages.

AB - Purpose: Children's Oncology Group defines very low-risk Wilms tumors (VLRWT) as stage I favorable histology Wilms tumors weighing less than 550 g in children younger than 24 months of age. VLRWTs may be treated with nephrectomy alone. However, 10% to 15% of VLRWTs relapse without chemotherapy. Previous studies suggest that VLRWTs with low WT1 expression and/or 11p15 loss of heterozygosity (LOH) may have increased risk of relapse. The current study validates these findings within prospectively identified children with VLRWT who did not receive adjuvant chemotherapy. Patients and Methods: Fifty-six VLRWTs (10 relapses) were analyzed for mutation of WT1, CTNNB1, and WTX; for 11p15 LOH using microsatellite analysis; and for H19DMR and KvDMR1 methylation. Results: 11p15 LOH was identified in 19 (41%) of 46 evaluable VLRWTs and was significantly associated with relapse (P < .001); 16 of 19 were isodisomic for 11p15. WT1 mutation was identified in nine (20%) of 45 evaluable VLRWTs and was significantly associated with relapse (P = .004); all nine cases also had 11p15 LOH. All evaluable tumors showing LOH by microsatellite analysis also showed LOH by methylation analysis. Retention of the normal imprinting pattern was identified in 24 of 42 evaluable tumors, and none relapsed. Loss of imprinting at 11p15 was identified in one of 42 tumors. Conclusion: WT1 mutation and 11p15 LOH are associated with relapse in patients with VLRWTs who do not receive chemotherapy. These may provide meaningful biomarkers to stratify patients for reduced chemotherapy in the future. VLRWTs show a different incidence of WT1 mutation and 11p15 imprinting patterns than has been reported in Wilms tumors of all ages.

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