BRAF mutations in metanephric adenoma of the kidney.
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
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 (e.g., p16 loss) in BRAF-driven oncogenesis.
Dana-Farber Cancer Institute, Boston, MA 02215, USA. toni_choueiri@dfci.harvard.edu
Toni K
TK
Choueiri
John
J
Cheville
Emanuele
E
Palescandolo
André P
AP
Fay
Philip W
PW
Kantoff
Michael B
MB
Atkins
Jesse K
JK
McKenney
Victoria
V
Brown
Megan E
ME
Lampron
Ming
M
Zhou
Michelle S
MS
Hirsch
Sabina
S
Signoretti
D000236:Adenoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis; D009154:Mutation; D009392:Nephrectomy; D010641:Phenotype; D010766:Phosphorylation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D019941:Cyclin-Dependent Kinase Inhibitor p16; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases