Human Genetics

, Volume 122, Issue 2, pp 117–127

High-density single nucleotide polymorphism array analysis in patients with germline deletions of 22q11.2 and malignant rhabdoid tumor

Authors

  • Eric M. Jackson
    • Department of NeurosurgeryUniversity of Pennsylvania School of Medicine
  • Tamim H. Shaikh
    • Division of Human Genetics and Molecular BiologyThe Children’s Hospital of Philadelphia
    • Department of PediatricsUniversity of Pennsylvania School of Medicine
  • Sridharan Gururangan
    • The Preston Robert Tisch Brain Tumor Center and the Departments of Pediatrics and SurgeryDuke University Medical Center
  • Marilyn C. Jones
    • Division of Dysmorphology and GeneticsRady Children’s Hospital
  • David Malkin
    • Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick ChildrenUniversity of Toronto
  • Sarah M. Nikkel
    • Department of GeneticsChildren’s Hospital of Eastern Ontario
  • Craig W. Zuppan
    • Department of PathologyLoma Linda University Medical Center
  • Luanne M. Wainwright
    • Division of Human Genetics and Molecular BiologyThe Children’s Hospital of Philadelphia
  • Fan Zhang
    • Division of Human Genetics and Molecular BiologyThe Children’s Hospital of Philadelphia
    • Division of Human Genetics and Molecular BiologyThe Children’s Hospital of Philadelphia
    • Department of PediatricsUniversity of Pennsylvania School of Medicine
    • The Children’s Hospital of Philadelphia, Abramson Research Building
Original Investigation

DOI: 10.1007/s00439-007-0386-3

Cite this article as:
Jackson, E.M., Shaikh, T.H., Gururangan, S. et al. Hum Genet (2007) 122: 117. doi:10.1007/s00439-007-0386-3

Abstract

Malignant rhabdoid tumors are highly aggressive neoplasms found primarily in infants and young children. The majority of rhabdoid tumors arise as a result of homozygous inactivating deletions or mutations of the INI1 gene located in chromosome band 22q11.2. Germline mutations of INI1 predispose to the development of rhabdoid tumors of the brain, kidney and extra-renal tissues, consistent with its function as a tumor suppressor gene. We now describe five patients with germline deletions in chromosome band 22q11.2 that included the INI1 gene locus, leading to the development of rhabdoid tumors. Two patients had phenotypic findings that were suggestive but not diagnostic for DiGeorge/Velocardiofacial syndrome (DGS/VCFS). The other three infants had highly aggressive disease with multiple tumors at the time of presentation. The extent of the deletions was determined by fluorescence in situ hybridization and high-density oligonucleotide based single nucleotide polymorphism arrays. The deletions in the two patients with features of DGS/VCFS were distal to the region typically deleted in patients with this genetic disorder. The three infants with multiple primary tumors had smaller but overlapping deletions, primarily involving INI1. The data suggest that the mechanisms underlying the deletions in these patients may be similar to those that lead to DGS/VCFS, as they also appear to be mediated by related, low copy repeats (LCRs) in 22q11.2. These are the first reported cases in which an association has been established between recurrent, interstitial deletions mediated by LCRs in 22q11.2 and a predisposition to cancer.

Supplementary material

439_2007_386_MOESM1_ESM.doc (24 kb)
Supplemental Table 1: Chromosomal positions of 22q11 LCRs (DOC 24.5 KB)
439_2007_386_MOESM2_ESM.doc (27 kb)
Supplemental Table 2: Deletion breakpoints in patients with germline 22q11.2 deletions (DOC 27 KB)

Copyright information

© Springer-Verlag 2007