Identification and high-resolution mapping of a constitutional 11q deletion in an infant with multifocal neuroblastoma

1These tumours are derived from the sympathetic nervous system and have a clinical phenotype that varies from localised benign tumours to aggressive, and often fatal, metastatic disease. This broad range of clinical behaviour reflects the biological heterogeneity of the tumour. 2 Several regions of the genome show patterns of somatically acquired aberrations in copy number, which are predictive of tumour behaviour. Amplification of the MYCN oncogene is often associated with unbalanced gain of 17q material and hemizygous deletion of 1p36. Tumours with this genotype typically show malignant progression. Deletions of 11q are rare in tumours with MYCN amplification but are also associated with increased metastatic potential and patients have decreased overall survival. 3,4 There is substantial evidence to suggest that 11q contains at least one neuroblastoma suppressor gene. 3,4 We have previously found that the genomic region most likely to be involved in allelic loss is located within 11q23–24 but the large size of most hemizygous deletions have prevented detection of a putative suppressor gene with traditional methods of genetic analysis. Germline chromosomal abnormalities, although rare in children with neuroblastoma, can help in the detection of tumour suppressor genes. In this case report, we identify a constitutional 11q deletion in an infant with multifocal neuroblastoma and describe the phenotype. The deletion boundaries were precisely mapped using high-resolution array-based comparative genomic hybridisation (aCGH) and PCR-based genotyping. These data provide unequivocal landmarks for chromosome-11 suppressor-gene identification. A 3-month-old male with multiple congenital abnormalities was referred to a paediatric oncology clinic for evaluation of an abdominal mass. A physical examination showed facial dysmorphism with a broad forehead, a flat nasal-bridge, bilateral parietal prominence, and hypertelorism. Other findings included a coloboma of the right iris, haemangiomas of the neck and chest, and hypotonia. An echocardiogram showed a double outlet right ventricle, a subaortic large ventricular septal defect, and subpulmonic stenosis. Other imaging studies also showed an absent corpus callosum with cortical atrophy, a horseshoe kidney with hydronephrosis, and a left adrenal tumour. The patient’s family history was remarkable—a maternal cousin had a congenital neuroblastoma and had been treated with surgery alone. Unfortunately, this tissue sample was not available for study and the maternal cousin was lost to follow-up. After surgical resection of the adrenal tumour, and a histopathological review of the resected tissue and other test results showing increased concentrations of urinary catecholamines, a diagnosis of neuroblastoma was made. At that time, the patient had no evidence of metastatic disease and his tumour had favourable biological characteristics, including a hyperdiploid DNA index, no evidence of a 1p36 deletion, no evidence of an unbalanced 17q gain, and no MYCN amplification. However, an 11q hemizygous deletion