Altered Structure and Expression of the Human Retinoblastoma Susceptibility Gene in Small Cell Lung Cancer

Charles H. Hensel, Chih Lin Hsieh, Susan L. Naylor, Alan Y. Sakaguchi, Adi F. Gazdar, Bruce E. Johnson, Wen Hwa Lee, Eva Y.H.P. Lee

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Abstract

Karyotypic and molecular genetic evidence has indicated that deletion or rearrangement of both chromosomes 3 and 13 may be important in the pathology of human small cell lung cancer (SCLC). The retinoblastoma susceptibility gene, RB, on chromosome 13 band ql4, has previously been shown to be altered in SCLC [J. W. Harbour et al., Science (Wash. DC), 241: 353–357, 1988; J. Yokota et al, Oncogene, 3: 471–475, 1988]. Our studies of 26 SCLC tumor and normal DNA samples indicate that 6 of 6 patients whose normal cell DNA was heterozygous for an RB restriction fragment length polymorphism have lost one of the two alleles in their tumor DNA. Consistent with other studies, we find 2 of 26 tumors with homozygous deletions within the RB gene. Of 13 SCLC cell lines examined, only 3 expressed greater than trace amounts of RB mRNA. RB protein was detected in 2 of 14 SCLC cell lines examined, unlike the results of Yokota et al. (Oncogene, 3:471–475, 1988) which showed no RB protein in any of the 9 cell lines they examined. Only unphosphory-lated RB protein was detected in SCLC cell line H209, suggesting that the RB protein may be inactivated by a novel mechanism in this cell line. These data suggest that inactivation of the RB gene is a frequent if not universal event in SCLC.

Original languageEnglish (US)
Pages (from-to)3067-3072
Number of pages6
JournalCancer Research
Volume50
Issue number10
StatePublished - May 15 1990

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hensel, C. H., Hsieh, C. L., Naylor, S. L., Sakaguchi, A. Y., Gazdar, A. F., Johnson, B. E., Lee, W. H., & Lee, E. Y. H. P. (1990). Altered Structure and Expression of the Human Retinoblastoma Susceptibility Gene in Small Cell Lung Cancer. Cancer Research, 50(10), 3067-3072.