Structural genome variations in individuals with childhood cancer and tumour predisposition syndromes

Saskia Hopman, Johannes Merks, Hubertus Eussen, Hannie Douben, Simone Snijder, Raoul Hennekam, Annelies de Klein, Huib Caron

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Previous studies have shown a high prevalence of syndromes in children with cancer. We described four patterns of co-occurring morphological abnormalities indicating new tumour predisposition syndromes. These patterns were named after their key-abnormalities: blepharophimosis (BP), epicanthal folds (EF), asymmetric lower limbs (LLA) and Sydney creases (SC) pattern. The purpose of our study was to identify structural genomic variants possibly involved in these tumour predisposition syndromes.

PATIENTS AND METHODS: In 49 probands (13 from BP, nine from EF, 20 from LLA and seven from SC patterns respectively) karyotyping was performed. Copy number variation (CNV) in genomic DNA of the probands was analysed to detect microdeletions/-duplications using SNP array. FISH and quantitative-polymerase chain reaction (q-PCR) experiments were done to validate events identified by cytogenetic and CNV analysis.

RESULTS: Cytogenetic analysis showed an inherited inversion of chromosome 15, inv(15) (q25q26) in a proband with LLA-pattern. Evaluation of the genes at the breakpoints made it unlikely that these explained the phenotype and tumour in this patient. Eleven CNV events met our inclusion criteria; three inherited CNV events involved an oncogene. A duplication involving BCL9 was identified in a proband diagnosed with Burkitt lymphoma. A duplication involving PCM1 was identified in a proband diagnosed with pre-B-ALL. Both probands showed the EF-pattern of morphological abnormalities. A deletion involving TRA@ was identified in two probands from the BP-pattern diagnosed with rhabdomyosarcoma and pre-B-ALL respectively.

CONCLUSIONS: We report on structural genomic variants in paediatric cancer patients with newly recognised tumour predisposition syndromes. We identify three CNV events which we suggest to be susceptibility loci.

Original languageEnglish
Pages (from-to)2170-8
Number of pages9
JournalEuropean journal of cancer (Oxford, England : 1990)
Issue number9
Publication statusPublished - Mar 2013
Externally publishedYes


  • Child
  • Chromosome Inversion/genetics
  • Congenital Abnormalities/genetics
  • Gene Duplication/genetics
  • Genetic Predisposition to Disease/genetics
  • Genome, Human/genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotype
  • Neoplasms/genetics
  • Polymorphism, Single Nucleotide/genetics
  • Precancerous Conditions/genetics
  • Real-Time Polymerase Chain Reaction
  • Syndrome


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