BRAF mutations in metanephric adenoma of the kidney

Toni K. Choueiri, John Cheville, Emanuele Palescandolo, André P. Fay, Philip W. Kantoff, Michael B. Atkins, Jesse K. McKenney, Victoria Brown, Megan E. Lampron, Ming Zhou, Michelle S. Hirsch, Sabina Signoretti

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Abstract

Background: Metanephric adenoma (MA) of the kidney is a rare, indolent tumor that may be difficult to differentiate from other small renal masses (SRMs). Genetic alterations associated with MA remain largely unknown. Objective: We aimed at defining genetic events in MA of the kidney and determining their influence in the management of this disease. Design, setting, and participants: Multiplexed mass spectrometric genotyping was performed on 29 MA cases after tumor DNA extraction. We also conducted a mutational screen in an additional 129 renal neoplasms. Immunohistochemistry was performed on the MA cases to assess molecular markers of signaling pathway activation. Patients' baseline characteristics, as well as follow-up data, were captured. Outcome measurements and statistical analysis: We used descriptive statistics for baseline clinical characteristics and incidence of mutations. The Wilcoxon rank-sum test was used to correlate patient characteristics with mutational status. Results and limitations: We identified the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation in 26 of 29 MA cases. These results were validated in all cases using the commercially available BRAF Pyro Kit (QIAGEN). In contrast, BRAF mutations were rare in the other 129 non-MA renal neoplasms that were screened. We detected a BRAF mutation (V600E) in only one papillary renal cell carcinoma case. In all MA tumors, we documented expression of phosphorylated mitogen-activated protein kinase and phosphorylated extracellular signal-regulated kinase, accompanied by immunoreactivity for p16 (INK4a). All patients were treated with a partial or radical nephrectomy, and after a median follow-up of 26.5 mo, there were no local or distant recurrences. Limitations include the retrospective nature of this study. Conclusions: BRAF V600E mutations are present in approximately 90% of all MA cases, serving as a potential valuable diagnostic tool in the differential diagnosis of SRMs undergoing a percutaneous biopsy. The presence of BRAF V600E and mitogen-activated protein kinase activation in a largely benign tumor supports the necessity for secondary events (eg, p16 loss) in BRAF-driven oncogenesis.

Original languageEnglish (US)
Pages (from-to)917-922
Number of pages6
JournalEuropean Urology
Volume62
Issue number5
DOIs
StatePublished - Nov 1 2012

Fingerprint

Adenoma
Kidney
Mutation
Kidney Neoplasms
Nonparametric Statistics
Mitogen-Activated Protein Kinases
Neoplasms
Extracellular Signal-Regulated MAP Kinases
Disease Management
Nephrectomy
Oncogenes
Renal Cell Carcinoma
Sarcoma
Carcinogenesis
Differential Diagnosis
Retrospective Studies
Immunohistochemistry
Biopsy
Recurrence
DNA

Keywords

  • BRAF
  • Diagnosis
  • Metanephric adenoma
  • Mutation
  • Small renal mass

ASJC Scopus subject areas

  • Urology

Cite this

Choueiri, T. K., Cheville, J., Palescandolo, E., Fay, A. P., Kantoff, P. W., Atkins, M. B., ... Signoretti, S. (2012). BRAF mutations in metanephric adenoma of the kidney. European Urology, 62(5), 917-922. https://doi.org/10.1016/j.eururo.2012.05.051

BRAF mutations in metanephric adenoma of the kidney. / Choueiri, Toni K.; Cheville, John; Palescandolo, Emanuele; Fay, André P.; Kantoff, Philip W.; Atkins, Michael B.; McKenney, Jesse K.; Brown, Victoria; Lampron, Megan E.; Zhou, Ming; Hirsch, Michelle S.; Signoretti, Sabina.

In: European Urology, Vol. 62, No. 5, 01.11.2012, p. 917-922.

Research output: Contribution to journalArticle

Choueiri, TK, Cheville, J, Palescandolo, E, Fay, AP, Kantoff, PW, Atkins, MB, McKenney, JK, Brown, V, Lampron, ME, Zhou, M, Hirsch, MS & Signoretti, S 2012, 'BRAF mutations in metanephric adenoma of the kidney', European Urology, vol. 62, no. 5, pp. 917-922. https://doi.org/10.1016/j.eururo.2012.05.051
Choueiri TK, Cheville J, Palescandolo E, Fay AP, Kantoff PW, Atkins MB et al. BRAF mutations in metanephric adenoma of the kidney. European Urology. 2012 Nov 1;62(5):917-922. https://doi.org/10.1016/j.eururo.2012.05.051
Choueiri, Toni K. ; Cheville, John ; Palescandolo, Emanuele ; Fay, André P. ; Kantoff, Philip W. ; Atkins, Michael B. ; McKenney, Jesse K. ; Brown, Victoria ; Lampron, Megan E. ; Zhou, Ming ; Hirsch, Michelle S. ; Signoretti, Sabina. / BRAF mutations in metanephric adenoma of the kidney. In: European Urology. 2012 ; Vol. 62, No. 5. pp. 917-922.
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abstract = "Background: Metanephric adenoma (MA) of the kidney is a rare, indolent tumor that may be difficult to differentiate from other small renal masses (SRMs). Genetic alterations associated with MA remain largely unknown. Objective: We aimed at defining genetic events in MA of the kidney and determining their influence in the management of this disease. Design, setting, and participants: Multiplexed mass spectrometric genotyping was performed on 29 MA cases after tumor DNA extraction. We also conducted a mutational screen in an additional 129 renal neoplasms. Immunohistochemistry was performed on the MA cases to assess molecular markers of signaling pathway activation. Patients' baseline characteristics, as well as follow-up data, were captured. Outcome measurements and statistical analysis: We used descriptive statistics for baseline clinical characteristics and incidence of mutations. The Wilcoxon rank-sum test was used to correlate patient characteristics with mutational status. Results and limitations: We identified the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation in 26 of 29 MA cases. These results were validated in all cases using the commercially available BRAF Pyro Kit (QIAGEN). In contrast, BRAF mutations were rare in the other 129 non-MA renal neoplasms that were screened. We detected a BRAF mutation (V600E) in only one papillary renal cell carcinoma case. In all MA tumors, we documented expression of phosphorylated mitogen-activated protein kinase and phosphorylated extracellular signal-regulated kinase, accompanied by immunoreactivity for p16 (INK4a). All patients were treated with a partial or radical nephrectomy, and after a median follow-up of 26.5 mo, there were no local or distant recurrences. Limitations include the retrospective nature of this study. Conclusions: BRAF V600E mutations are present in approximately 90{\%} of all MA cases, serving as a potential valuable diagnostic tool in the differential diagnosis of SRMs undergoing a percutaneous biopsy. The presence of BRAF V600E and mitogen-activated protein kinase activation in a largely benign tumor supports the necessity for secondary events (eg, p16 loss) in BRAF-driven oncogenesis.",
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AU - Cheville, John

AU - Palescandolo, Emanuele

AU - Fay, André P.

AU - Kantoff, Philip W.

AU - Atkins, Michael B.

AU - McKenney, Jesse K.

AU - Brown, Victoria

AU - Lampron, Megan E.

AU - Zhou, Ming

AU - Hirsch, Michelle S.

AU - Signoretti, Sabina

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N2 - Background: Metanephric adenoma (MA) of the kidney is a rare, indolent tumor that may be difficult to differentiate from other small renal masses (SRMs). Genetic alterations associated with MA remain largely unknown. Objective: We aimed at defining genetic events in MA of the kidney and determining their influence in the management of this disease. Design, setting, and participants: Multiplexed mass spectrometric genotyping was performed on 29 MA cases after tumor DNA extraction. We also conducted a mutational screen in an additional 129 renal neoplasms. Immunohistochemistry was performed on the MA cases to assess molecular markers of signaling pathway activation. Patients' baseline characteristics, as well as follow-up data, were captured. Outcome measurements and statistical analysis: We used descriptive statistics for baseline clinical characteristics and incidence of mutations. The Wilcoxon rank-sum test was used to correlate patient characteristics with mutational status. Results and limitations: We identified the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation in 26 of 29 MA cases. These results were validated in all cases using the commercially available BRAF Pyro Kit (QIAGEN). In contrast, BRAF mutations were rare in the other 129 non-MA renal neoplasms that were screened. We detected a BRAF mutation (V600E) in only one papillary renal cell carcinoma case. In all MA tumors, we documented expression of phosphorylated mitogen-activated protein kinase and phosphorylated extracellular signal-regulated kinase, accompanied by immunoreactivity for p16 (INK4a). All patients were treated with a partial or radical nephrectomy, and after a median follow-up of 26.5 mo, there were no local or distant recurrences. Limitations include the retrospective nature of this study. Conclusions: BRAF V600E mutations are present in approximately 90% of all MA cases, serving as a potential valuable diagnostic tool in the differential diagnosis of SRMs undergoing a percutaneous biopsy. The presence of BRAF V600E and mitogen-activated protein kinase activation in a largely benign tumor supports the necessity for secondary events (eg, p16 loss) in BRAF-driven oncogenesis.

AB - Background: Metanephric adenoma (MA) of the kidney is a rare, indolent tumor that may be difficult to differentiate from other small renal masses (SRMs). Genetic alterations associated with MA remain largely unknown. Objective: We aimed at defining genetic events in MA of the kidney and determining their influence in the management of this disease. Design, setting, and participants: Multiplexed mass spectrometric genotyping was performed on 29 MA cases after tumor DNA extraction. We also conducted a mutational screen in an additional 129 renal neoplasms. Immunohistochemistry was performed on the MA cases to assess molecular markers of signaling pathway activation. Patients' baseline characteristics, as well as follow-up data, were captured. Outcome measurements and statistical analysis: We used descriptive statistics for baseline clinical characteristics and incidence of mutations. The Wilcoxon rank-sum test was used to correlate patient characteristics with mutational status. Results and limitations: We identified the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation in 26 of 29 MA cases. These results were validated in all cases using the commercially available BRAF Pyro Kit (QIAGEN). In contrast, BRAF mutations were rare in the other 129 non-MA renal neoplasms that were screened. We detected a BRAF mutation (V600E) in only one papillary renal cell carcinoma case. In all MA tumors, we documented expression of phosphorylated mitogen-activated protein kinase and phosphorylated extracellular signal-regulated kinase, accompanied by immunoreactivity for p16 (INK4a). All patients were treated with a partial or radical nephrectomy, and after a median follow-up of 26.5 mo, there were no local or distant recurrences. Limitations include the retrospective nature of this study. Conclusions: BRAF V600E mutations are present in approximately 90% of all MA cases, serving as a potential valuable diagnostic tool in the differential diagnosis of SRMs undergoing a percutaneous biopsy. The presence of BRAF V600E and mitogen-activated protein kinase activation in a largely benign tumor supports the necessity for secondary events (eg, p16 loss) in BRAF-driven oncogenesis.

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KW - Mutation

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