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Science 15 July 1988:
Vol. 241. no. 4863, pp. 353 - 357
DOI: 10.1126/science.2838909
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Articles

Science, Vol 241, Issue 4863, 353-357
Copyright © 1988 by American Association for the Advancement of Science

articles

Abnormalities in structure and expression of the human retinoblastoma gene in SCLC

JW Harbour, SL Lai, J Whang-Peng, AF Gazdar, JD Minna, and FJ Kaye

Howard Hughes Medical Institute, Bethesda, MD 20814.

Small cell lung cancer (SCLC) has been associated with loss of heterozygosity at several distinct genetic loci including chromosomes 3p, 13q, and 17p. To determine whether the retinoblastoma gene (Rb) localized at 13q14, might be the target of recessive mutations in lung cancer, eight primary SCLC tumors and 50 cell lines representing all major histologic types of lung cancer were examined with the Rb complementary DNA probe. Structural abnormalities within the Rb gene were observed in 1/8 (13%) primary SCLC tumors, 4/22 (18%) SCLC lines, and 1/4 (25%) pulmonary carcinoid lines (comparable to the 20 to 40% observed in retinoblastoma), but were not detected in other major types of lung cancer. Rb messenger RNA expression was absent in 60% of the SCLC lines and 75% of pulmonary carcinoid lines, including all samples with DNA abnormalities. In contrast, Rb transcripts were found in 90% of non-SCLC lung cancer lines and in normal human lung. The finding of abnormalities of the Rb gene in SCLC and pulmonary carcinoids (both neuroendocrine tumors) suggests that this gene may be involved in the pathogenesis of a common adult malignancy.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)