Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma.
Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma.
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DOI：
10.1001/jama.1995.03520310056030
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发表时间：
1995-02
期刊：
影响因子：
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通讯作者：
Jaclyn Y. Hung;Yosuke Kishimoto;Kenji Sugio;A. Virmani;Donald D. McIntire;J. Minna;A. Gazdar
中科院分区：
文献类型：
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作者：
Jaclyn Y. Hung;Yosuke Kishimoto;Kenji Sugio;A. Virmani;Donald D. McIntire;J. Minna;A. Gazdar
背景技术大多数肺癌中都存在 3 号染色体短臂 (3p) 的缺失。目的探讨染色体3p缺失在非小细胞肺癌发病机制中的作用。设计 研究了七个档案、石蜡包埋、手术切除的肺癌标本。从染色的载玻片上显微解剖出 50 个精确鉴定的支气管、细支气管和肺泡中存在的恶性和肿瘤前病变，并使用基于聚合酶链反应的三个染色体 3p 位点（3p14、3p21.3 和 3p25）的二核苷酸重复多态性分析来分析等位基因丢失。设置 大学医疗中心和附属医院。对象 分析了 7 名因非小细胞肺癌而接受手术切除的患者的样本，这些患者的样本包括广泛的多灶性癌前病变区域（增生、化生、不典型增生或非浸润性癌症）。结果 对于所分析的所有三个微卫星，来自所有七个病例的淋巴细胞都是杂合的（即，信息丰富）。七种侵袭性癌症中有六种 (86%) 在一个或多个染色体 3p 位点上发生杂合性丢失。在伴随的肿瘤前病变中，两个正常细支气管中均未检测到杂合性丢失，17 个增生中的 13 个（76%）、7 个不典型增生中的 6 个（86%）以及 4 个非侵袭性癌症中的 4 个（100%）均未检测到杂合性丢失。在整个呼吸道、支气管、细支气管和肺泡中均检测到杂合性丢失。在 23 个癌前病变中的 18 个（78%）中，丢失的特定等位基因与相应癌症中丢失的特定等位基因相同。这种情况偶然发生的概率是 5.3 x 10(-3)。结论 3号染色体短臂缺失发生在肺癌发病机制的最早阶段（增生），并涉及呼吸道的所有区域。等位基因丢失具有高度特异性，但其机制仍不清楚。我们的发现可能具有相当大的生物学、预后和临床意义。
BACKGROUND Deletions in the short arm of chromosome 3 (3p) are present in most lung carcinomas. OBJECTIVE To investigate the role of these chromosome 3p deletions in the pathogenesis of non-small cell lung carcinomas. DESIGN Seven archival, paraffin-embedded, surgically resected lung cancer specimens were studied. Fifty precisely identified malignant and preneoplastic lesions present in bronchi, bronchioles, and alveoli were microdissected from stained slides and analyzed for allele loss using polymerase chain reaction-based assays for dinucleotide repeat polymorphisms at three chromosome 3p loci (3p14, 3p21.3, and 3p25). SETTING University-based medical center and affiliated hospitals. SUBJECTS Samples were analyzed from seven patients who underwent surgical resection with curative intent for non-small cell lung cancer and whose specimens included extensive multifocal areas of preneoplastic lesions (hyperplasia, metaplasia, dysplasia, or noninvasive cancer). RESULTS Lymphocytes from all seven cases were heterozygous (ie, informative) for all three microsatellites analyzed. Six (86%) of seven invasive cancers had loss of heterozygosity at one or more chromosome 3p sites. In the accompanying preneoplastic lesions, loss of heterozygosity was detected in none of two normal bronchioles, 13 (76%) of 17 hyperplasias, six (86%) of seven dysplasias, and four (100%) of four noninvasive cancers. Loss of heterozygosity was detected throughout the respiratory tract, in bronchi, bronchioles, and alveoli. In 18 (78%) of 23 preneoplastic lesions, the specific alleles lost were identical to those lost in the corresponding carcinomas. The probability of this happening by chance is 5.3 x 10(-3). CONCLUSIONS Deletions in the short arm of chromosome 3 occur at the earliest stage (hyperplasia) in the pathogenesis of lung cancer and involve all regions of the respiratory tract. Allele loss is highly specific, but its mechanism remains unknown. Our findings may be of considerable biologic, prognostic, and clinical significance.