Exclusion of APC and VHL gene deletions by array-based comparative hybridization in two patients with microscopically visible chromosomal aberrations

Abstract Karyotyping is a major component of the genetic work-up of patients with dysmorphism. Cytogenetic aberrations close to a known tumor suppressor gene raise important clinical issues because deletion of that tumor suppressor gene can cause genetic predisposition to cancer. We present two canc...

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Bibliographic Details
Published in:Cancer genetics and cytogenetics 2007-10, Vol.178 (2), p.151-154
Main Authors: Wallerstein, Robert J, Brooks, Susan Sklower, Streck, Deanna L, Kurvathi, Rohini, Toruner, Gokce A
Format: Article
Language:English
Subjects:
Adenomatous Polyposis Coli - genetics
Adolescent
Adult
Chromosome Aberrations
Female
Genes, APC
Hematology, Oncology and Palliative Medicine
Humans
Medical Education
Nucleic Acid Hybridization
Oligonucleotide Array Sequence Analysis
Sequence Deletion
von Hippel-Lindau Disease - genetics
Von Hippel-Lindau Tumor Suppressor Protein - genetics
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Summary:Abstract Karyotyping is a major component of the genetic work-up of patients with dysmorphism. Cytogenetic aberrations close to a known tumor suppressor gene raise important clinical issues because deletion of that tumor suppressor gene can cause genetic predisposition to cancer. We present two cancer-free dysmorphic patients with karyotypes of 46,XX,del(5)(q15q22.3) and 46,XX,del(3)(p25.2∼pter). These deletions are close to the APC and VHL genes that confer susceptibility to familial Adenomatous polyposis (OMIM #17510) and von-Hippel-Lindau syndrome (OMIM #193300), respectively. The array-based comparative genomic hybridization (array-CGH) analysis using a custom Agilent 44K oligonucleotide array demonstrated an interstitial 20.7-megabase (Mb) deletion on 5q (chr5: 89,725,638-110,491,345) and a terminal 9.45-Mb deletion on 3p (chr3:pter-9,450,984). According to the March 2006 human reference sequence, the APC gene is located at chr5: 112,101,483-112,209,835 and the VHL gene is located at chr3: 10,158,319-10,168,746. These results indicate that the APC gene is 2,300 kilobases (kb) and the VHL gene is 700 kb away from deleted regions. Southern blot analysis for APC and VHL genes were negative, consistent with array-CGH findings. These results demonstrate the power of array-CCH to assess potential tumor suppressor gene involvement and cancer risk in patients with microscopically visible deletions in areas near tumor suppressors.
ISSN:0165-4608
1873-4456
DOI:10.1016/j.cancergencyto.2007.07.014