Harbour J W, Lai S L, Whang-Peng J, Gazdar A F, Minna J D, Kaye F J
Howard Hughes Medical Institute, Bethesda, MD 20814.
Science. 1988 Jul 15;241(4863):353-7. doi: 10.1126/science.2838909.
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.
小细胞肺癌（SCLC）与几个不同基因位点的杂合性缺失有关，这些位点包括染色体3p、13q和17p。为了确定定位于13q14的视网膜母细胞瘤基因（Rb）是否可能是肺癌隐性突变的靶点，使用Rb互补DNA探针检测了8例原发性SCLC肿瘤和50个代表所有主要组织学类型肺癌的细胞系。在1/8（13%）的原发性SCLC肿瘤、4/22（18%）的SCLC细胞系和1/4（25%）的肺类癌细胞系中观察到Rb基因的结构异常（与视网膜母细胞瘤中观察到的20%至40%相当），但在其他主要类型的肺癌中未检测到。60%的SCLC细胞系和75%的肺类癌细胞系中不存在Rb信使RNA表达，包括所有有DNA异常的样本。相比之下，在90%的非SCLC肺癌细胞系和正常人类肺组织中发现了Rb转录本。在SCLC和肺类癌（均为神经内分泌肿瘤）中发现Rb基因异常表明，该基因可能参与一种常见成人恶性肿瘤的发病机制。
