title: Constitutional 560.49 kb chromosome 2p24.3 duplication including the MYCN gene identified by SNP chromosome microarray analysis in a child with multiple congenital anomalies and bilateral Wilms tumor.
abstract: Fewer than 100 patients with partial chromosome 2p trisomy have been reported. Clinical features are variable and depend on the size of the duplicated segment, but generally include psychomotor delay, facial anomalies, congenital heart defect, and other abnormalities. We report a 560.49 kb duplication of chromosome 2p in a 13 month-old male with hydrocephaly, ventricular septal defect, partial agenesis of the corpus callosum, and bilateral Wilms tumor. After discovery of bilateral renal masses at four months of age, the child underwent neoadjuvant chemotherapy followed by right radical nephrectomy that revealed triphasic Wilms' tumor. A needle core biopsy on one of two lesions on the left kidney also revealed Wilms tumor. A partial left nephrectomy revealed focally positive margins that necessitated left flank radiotherapy. The tumor karyotype was 46,XY,t(7;8)(q36;p11)[8]/46,XY [12] while his constitutional karyotype was 46,XY, suggesting that the t(7;8)(q36;p11) was associated with the malignancy. Single nucleotide polymorphism (SNP) chromosome microarray analysis of peripheral blood identified a maternally-inherited 560.49 kb chromosome 2p24.3 duplication that involved four OMIM genes: NBAS, DDX1, MYCNOS, and MYCN. SNP array analysis of the tumor revealed the same 2p24.3 duplication. At present, the now 5-year-old boy continues to do well without clinical or radiographic evidence of recurrent disease. This case is instructive because the child's health insurer initially denied authorization for chromosome microarray analysis (CMA), and it took more than one year before such authorization was finally granted. That initial decision to deny coverage could have had untoward health implications for this child, as the identification of constitutional MYCN duplication necessitated surveillance imaging for a number of pediatric malignancies associated with MYCN overexpression/dysregulation.
authors: Department of Pathology and Laboratory Medicine, Beaumont Health, Royal Oak, MI, USA; Oakland University William Beaumont School of Medicine, Rochester, MI, USA. Electronic address: mmicale@beaumont.edu.
authors: Mark A
authors: MA
authors: Micale
authors: Department of Pathology and Laboratory Medicine, Beaumont Health, Royal Oak, MI, USA.
authors: Bedford
authors: B
authors: Embrey
authors: Department of Pathology and Laboratory Medicine, Beaumont Health, Royal Oak, MI, USA; Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
authors: Jacqueline K
authors: JK
authors: Macknis
authors: Beaumont Children's Hospital, Royal Oak, MI, USA; Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
authors: Cheryl E
authors: CE
authors: Harper
authors: Beaumont Children's Hospital, Royal Oak, MI, USA; Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
authors: David J
authors: DJ
authors: Aughton
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D058674:Chromosome Duplication / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D006801:Humans; D007223:Infant; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D000071447:N-Myc Proto-Oncogene Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014314:Trisomy / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein
keywords: 2p24.3 microduplication; MYCN gene; SNP array; Wilms tumor