p53 mutation spectra for squamous cell carcinomas at different levels of human bronchial branches
p53 mutation spectra for squamous cell carcinomas at different levels of human bronchial branches
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DOI：
10.1002/ijc.21877
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发表时间：
2006-08
影响因子：
6.4
通讯作者：
Takuo Shimmyo;T. Hashimoto;Yasuhito Kobayashi;Y. Miyagi;Y. Ishikawa;K. Nakagawa;H. Osada;E. Tsuchiya
中科院分区：
文献类型：
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作者：
Takuo Shimmyo;T. Hashimoto;Yasuhito Kobayashi;Y. Miyagi;Y. Ishikawa;K. Nakagawa;H. Osada;E. Tsuchiya
肺不同部位发生的鳞状细胞癌（SCC）是否由不同的病因引起的问题对于预防、早期发现和有效治疗具有明显的重要性。我们在此将大量切除的SCC（74例）细分为3个肿瘤部位，中央（主支气管至段支气管），中间（亚段至亚段支气管）和外周（亚段支气管远端），并检查与p53突变谱和吸烟史的关系，以提供病因因素的线索。尽管重度吸烟者的比例最高，但中央病变（40%）中CpG位点的G→A转换率被认为是由内源性机制引起的，高于中间病变（0%）和外周病变（14%）。与此相反，与烟草烟雾致癌物相关的G→T颠换在中间位置最常见（50%），尽管仅限于p53突变病例时，重度吸烟者的比例在这些位置之间是相同的。在外周，其他突变最高（67%），而在中心和中间区域分别为33%和50%。因此，不同的病因可能在支气管树不同部位的SCC的发展中起着因果作用。此外，研究结果表明，更广泛的研究烟草烟雾致癌物对内源性机制的影响是必要的。© 2006 Wiley利斯公司
The question of whether squamous cell carcinomas (SCCs) arising in different sites of lung are caused by different etiological factors is of obvious importance for prevention, early detection and effective treatment. We here subclassified a large series of resected SCCs (74 cases) into 3 tumor‐sites, central (main to segmental bronchi), intermediate (subsegmental to sub‐subsegmental) and peripheral (distal to sub‐subsegmental bronchi), and examined relationships with p53 mutational spectra and smoking history to provide clues to etiological factors. The rate for G→A transitions at CpG sites considered to be caused by endogenous mechanism was higher in central (40%) than in intermediate (0%) and peripheral (14%) lesions, in spite of highest percentage of heavy smokers. In contrast, G→T transversions associated with tobacco smoke carcinogens were most frequent (50%) in the intermediate location, although proportions of heavy smoker's ratio were the same among the locations when confined to p53 mutation cases. In the periphery, other mutations were highest (67%) compared with 33 and 50% in the central and intermediate regions, respectively. Thus, different etiological factors may be playing causal roles in the development of SCCs in different locations of bronchial tree. Furthermore, the results suggest that more extensive study of the influence of tobacco smoke carcinogens on endogenous mechanisms is warranted. © 2006 Wiley‐Liss, Inc.