Center R, Lukeis R, Dietzsch E, Gillespie M, Garson O M
Department of Cytogenetics, St. Vincent's Hospital, Fitzroy, Australia.
Genes Chromosomes Cancer. 1993 May;7(1):47-53. doi: 10.1002/gcc.2870070108.
Previously we have reported non-random cytogenetic abnormalities involving the short arm of chromosome 9 (9P) in the majority of primary non-small cell lung cancer (NSCLC) patient samples, which indicated loss of DNA sequences. In another lung tumor, pleural malignant mesothelioma (MM), cytogenetic changes also include apparent deletions of 9p. To define the location and extent of deletions of 9p in NSCLC and MM, Southern blot analyses on six NSCLC and five MM cell lines using molecular probes to 9p loci (IFNA, IFNB1, D9S3, and D9S19) were performed, and DNA dosage was determined by densitometry. Our data demonstrated reduced dosage of 9p sequences in three of six NSCLC and four of five MM lines. A homozygous deletion of D9S3 was found in one NSCLC and one MM cell line. The region of common loss overlapped the D9S3 locus and was flanked by the IFNB1 and D9S19 loci. IFNB as previously been localized to 9p22, and the D9S3 and D9S19 loci have been mapped in this study by in situ hybridization to 9p21 and 9p13, respectively. We hypothesize the existence of one or more tumor suppressor genes on 9p with a role in the development or progression of NSCLC and MM.
此前我们报道过，在大多数原发性非小细胞肺癌（NSCLC）患者样本中存在涉及9号染色体短臂（9p）的非随机细胞遗传学异常，这表明存在DNA序列缺失。在另一种肺肿瘤——胸膜恶性间皮瘤（MM）中，细胞遗传学改变也包括9p的明显缺失。为了确定NSCLC和MM中9p缺失的位置和范围，我们使用针对9p位点（IFNA、IFNB1、D9S3和D9S19）的分子探针，对6个NSCLC细胞系和5个MM细胞系进行了Southern印迹分析，并通过密度测定法确定DNA剂量。我们的数据表明，6个NSCLC细胞系中有3个以及5个MM细胞系中有4个的9p序列剂量减少。在1个NSCLC细胞系和1个MM细胞系中发现了D9S3的纯合缺失。共同缺失区域与D9S3位点重叠，两侧分别为IFNB1和D9S19位点。IFNB先前已定位到9p22，在本研究中，D9S3和D9S19位点分别通过原位杂交定位到9p21和9p13。我们推测9p上存在一个或多个肿瘤抑制基因，它们在NSCLC和MM的发生或发展中起作用。
