Confirmation of Xp22.11 Duplication as a Germline Susceptibility Alteration in a Wilms Tumor Arising in Horseshoe Kidney

Abstract Background There is strong evidence of a genetic contribution to Wilms tumor, such as WT1 gene variation or epigenetic changes at chromosome locus 11p15. A previous genome wide association study (GWAS) of Wilms tumor identified other significant association loci including Xp22. Case report: A 4-year-old girl developed a Wilms tumor of the left isthmus of a horseshoe kidney. Chromosomal microarray analysis (CMA) of peripheral blood showed a 563 kb copy number gain at Xp22.11 that included PRDX4 and ZFX. PRDX4 has been shown to play an active role in the tumorigenesis of malignant neoplasms in various organs. Beckwith-Wiedemann methylation analysis and WT1 sequencing were negative. Whole exome sequencing of peripheral blood revealed pathogenic variant in PMS2 gene (c.765C > A), which is consistent with Lynch syndrome. Conclusion: We report a case of Wilms tumor with germline Xp22.11 duplication which further supports this locus as germline susceptibility alteration for Wilms Tumor.

[1]  S. Robertson,et al.  Wilms tumor in patients with osteopathia striata with cranial sclerosis , 2020, European Journal of Human Genetics.

[2]  Dong-Seok Lee,et al.  Interplay Between Mitochondrial Peroxiredoxins and ROS in Cancer Development and Progression , 2019, International journal of molecular sciences.

[3]  M. Harris,et al.  Clinical, Pathologic, and Genetic Features of Wilms Tumors With WTX Gene Mutation , 2017, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[4]  J. Dome,et al.  Wilms Tumor Predisposition , 2016 .

[5]  Richard A. Moore,et al.  Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report from the Children's Oncology Group , 2016, Clinical Cancer Research.

[6]  N. Sebire,et al.  Wilms’ Tumour – Histology and Differential Diagnosis , 2016 .

[7]  N. Olgun,et al.  Tissue Expression of MLH1, PMS2, MSH2, and MSH6 Proteins and Prognostic Value of Microsatellite Instability in Wilms Tumor: Experience of 45 Cases , 2013, Pediatric hematology and oncology.

[8]  H. Zhang,et al.  Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9 , 2012, Cancer Gene Therapy.

[9]  S. Seal,et al.  A genome-wide association study identifies susceptibility loci for Wilms tumor , 2012, Nature Genetics.

[10]  Ying Liang,et al.  Identification of PRDX4 and P4HA2 as metastasis-associated proteins in oral cavity squamous cell carcinoma by comparative tissue proteomics of microdissected specimens using iTRAQ technology. , 2011, Journal of proteome research.

[11]  E. Kuipers,et al.  Biallelic germline mutations of mismatch‐repair genes , 2007, Cancer.

[12]  V. Huff,et al.  Familial Wilms tumor , 2004, American journal of medical genetics. Part C, Seminars in medical genetics.

[13]  Y. Tsunematsu,et al.  A Novel Case of Wilms’ Tumor Followed by Colon Cancer, Both Showing Microsatellite Instability , 2000, Oncology.

[14]  A. Jacobs.  HORSESHOE KIDNEY , 1930, British medical journal.