Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma

Mellone N. Marchong, Danian Chen, Timothy Corson, Cheong Lee, Maria Harmandayah, Ella Bowles, Ning Chen, Brenda L. Gallie

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Retinoblastoma is initiated by loss of both RB1 alleles. Previous studies have shown that retinoblastoma tumors also show further genomic gains and losses. We now define a 2.62 Mbp minimal region of genomic loss of chromosome 16q22, which is likely to contain tumor suppressor gene(s), in 76 retinoblastoma tumors, using loss of heterozygosity (30 of 76 tumors) and quantitative multiplex PCR (71 of 76 tumors). The sequence-tagged site WI-5835 within Intron 2 of the cadherin-11 (CDH11) gene showed the highest frequency of loss (54%, 22 of 41 samples tested). A second hotspot for loss (39%, 9 of 23 samples tested) was detected within intron 2 of the cadherin-13 (CDH13) gene. Furthermore, deletion of the exons of CDH11 and/or WI-5835 was shown by quantitative multiplex PCR in 17 of 30 (57%) of previously untested tumors, Immunoblot analyses revealed that 91% (20 of 22) retinoblastoma exhibited either a complete loss or a decrease of the intact form of CDH11 and 8 of 13 showed a prevalent band suggestive of the variant form. Copy number of WI-5835 for these samples correlated with CDH11 protein expression. CDH11 staining was evident in the inner nuclear layer in early mouse retinal development and in small transgenic murine SV40 large T antigen-induced retinoblastoma tumors, but advanced tumors frequently showed loss of CDH11 expression by reverse transcription-PCR, suggestive of a role for CDH11 in tumor progression or metastasis. CDH13 protein and mRNA were consistently expressed in all human and murine retinoblastoma compared with normal adult human retina. Our analyses implicate CDH11, but not CDH13, as a potential tumor suppressor gene in retinoblastoma.

Original languageEnglish (US)
Pages (from-to)495-503
Number of pages9
JournalMolecular Cancer Research
Volume2
Issue number9
StatePublished - Sep 2004
Externally publishedYes

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Retinoblastoma
Neoplasms
Multiplex Polymerase Chain Reaction
Tumor Suppressor Genes
Introns
Sequence Tagged Sites
Polyomavirus Transforming Antigens
osteoblast cadherin
Loss of Heterozygosity
Viral Tumor Antigens
Genes
Reverse Transcription
Retina
Exons
Proteins
Chromosomes
Alleles
Staining and Labeling
Neoplasm Metastasis
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Marchong, M. N., Chen, D., Corson, T., Lee, C., Harmandayah, M., Bowles, E., ... Gallie, B. L. (2004). Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma. Molecular Cancer Research, 2(9), 495-503.

Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma. / Marchong, Mellone N.; Chen, Danian; Corson, Timothy; Lee, Cheong; Harmandayah, Maria; Bowles, Ella; Chen, Ning; Gallie, Brenda L.

In: Molecular Cancer Research, Vol. 2, No. 9, 09.2004, p. 495-503.

Research output: Contribution to journalArticle

Marchong, MN, Chen, D, Corson, T, Lee, C, Harmandayah, M, Bowles, E, Chen, N & Gallie, BL 2004, 'Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma', Molecular Cancer Research, vol. 2, no. 9, pp. 495-503.
Marchong MN, Chen D, Corson T, Lee C, Harmandayah M, Bowles E et al. Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma. Molecular Cancer Research. 2004 Sep;2(9):495-503.
Marchong, Mellone N. ; Chen, Danian ; Corson, Timothy ; Lee, Cheong ; Harmandayah, Maria ; Bowles, Ella ; Chen, Ning ; Gallie, Brenda L. / Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma. In: Molecular Cancer Research. 2004 ; Vol. 2, No. 9. pp. 495-503.
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