Clinical, Pathologic, and Genetic Features of Wilms Tumors With WTX Gene Mutation.
Clinical and pathologic features of patients with WTX-mutated Wilms tumor (WT) have not been studied in detail. We characterize the clinical and pathologic findings in WT with WTX abnormalities and provide comparison with WT without WTX mutation. Clinical, gross, and microscopic features in 35 patients with WT were examined. Karyotype was examined in a subset of cases. All cases had been previously analyzed for WTX, WT1, and CTNNB1 aberrations via array comparative genomic hybridization; OncoMap 4 high throughput genotyping was performed on 18 cases. Eleven tumors had WTX abnormality. No significant differences were identified between patients with mutated versus nonmutated WTX with respect to gender (45% versus 33% male), age (mean 3.9 versus 4.1 years), tumor size (mean 12.7 cm versus 12.8 cm), anaplasia (9% versus 12%), rhabdomyoblastic differentiation (18% versus 8%), cartilage differentiation (9% versus 4%), mucinous epithelial differentiation (9% versus 4%), nephrogenic rests (28% versus 21%), or relapse rate (11% versus 25%). Mutations in KRAS, MYC, and PIK3R1 were restricted to WTX-mutated WT, mutations in AKT, CKDN2A, EFGR, HRAS, MET, and RET were restricted to WT without WTX mutation, and mutations in BRAF, CTTNB1, NRAS, PDGFRA, and STK11 were seen in both groups. Our study revealed no clinical or pathologic distinctions between WT with and without WTX abnormality. This similarity lends support to the concept of a common tumorigenic pathway between WT with aberrant WTX and those without.
1 Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.|2 Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Sanda
S
Alexandrescu
3 Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Sara
S
Akhavanfard
1 Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.|2 Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Marian H
MH
Harris
1 Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.|2 Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Sara O
SO
Vargas
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D060005:Genotyping Techniques; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*
C517118:AMER1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins
OncoMap; WT1; WTX; Wilms tumor; somatic mutation