Alterations in p16 and p53 genes and chromosomal findings in patients with lung cancer: Fluorescence in situ hybridization and cytogenetic studies
Alterations in p16 and p53 genes and chromosomal findings in patients with lung cancer: Fluorescence in situ hybridization and cytogenetic studies
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DOI：
10.1016/j.canep.2010.03.018
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发表时间：
2010-08-01
影响因子：
2.6
通讯作者：
Hanta, Ismail
中科院分区：
文献类型：
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作者：
Demirhan, Osman;Tastemir, Deniz;Hanta, Ismail
背景染色体异常和基因不稳定(S)是与癌细胞遗传不稳定性有关的两个因素。p16和p53基因的抑癌功能丧失是导致人类癌症发生的最常见事件。肺癌是世界上导致癌症死亡的主要原因。肺癌的染色体异常可能为识别靶基因提供有价值的线索，并最终成功寻找主要基因。本研究应用荧光原位杂交(FISH)技术和细胞遗传学方法，对小细胞肺癌和非小细胞肺癌患者的p16、p53基因突变和染色体异常进行研究。结果肺癌组织中p16基因和p53基因的缺失频率较高，分别为8/18(44%)和7/18(39%)。18例肺癌患者中，18例患者均表现出以数目和结构异常为主的结构异常，结构异常主要表现为各种染色体的缺失、断裂和脆性，几乎所有患者均可观察到结构和数目异常。9和8个常染色体非整倍体也是最常见的(22、19、18、20、9和17号染色体)。结论DNA损伤和基因组不稳定性可能是肺癌发生、发展的重要因素。肺癌患者除染色体异常外，p16和p53基因缺失的频率较高，烟草可能是肺癌发生发展的主要致癌因素。爱思唯尔有限公司代表国际预防肿瘤学学会出版的
Background Chromosomal aberrations and instability of gene(s) are two factors related to the genetic instability of cancer cells A loss of the tumor-suppressor function of the genes p16 and p53 is the most common event leading to the development of human cancers Carcinoma of the lung is the leading cause of cancer deaths in the world Chromosomal abnormalities in lung cancer may provide a valuable clue to the identification of target loci and culminate in a successful search for the major genes. The aim of this study was to investigate (i) alterations of the p16 and p53 genes and (ii) chromosomal aberrations in patients with small cell and non-small cell lung cancer by fluorescence in situ hybridization (FISH) and cytogenetic studies Methods We carried out cytogenetic analysis by Giemsa-banding in 18 cases. FISH probes for the p16 and p53 genes were also used on interphase nuclei to screen the alterations in these genes in lung cancer (LC) Results We observed a high frequency of losses of the p16 - in 8/18(44%) - and p53 - in 7/18 (39%) - genes in the cases with LC A total of 18 patients showed predominantly numerical and structural aberrations Among these two types, structural aberrations predominated and usually consisted of deletions, breaks, and fragilities in various chromosomes Both structural and numerical changes weir observed in almost all patients Chromosomes 3 and 1 were found to be most frequently involved in structural abnormalities, followed by chromosomes 6, 9, and 8 Autosomal aneuploidies were also observed to be the most frequent (chromosomes 22, 19, 18, 20, 9, and 17). followed by those of the X and Y chromosomes The expression of fragile sites was also found to be significantly higher in seven chromosomal regions 3p14, 1q21, 1q12, 6q26, 9q13, 8q22, and 8q24 Conclusion Our data confirmed that DNA damage and genomic instability may be factors contributing to the mutation profile and development of lung cancer The patients who developed lung cancer showed a high frequency of loss of both p16 and p53, in addition to chromosomal aberrations Tobacco could be a major carcinogenic factor in lung-cancer progression The loss of p16 and p53, and increased incidence of autosomal aneuploidy and chromatid breaks, along with other chromosomal alterations, can contribute to the progression of the disease Published by Elsevier Ltd on behalf of International Society of Preventive Oncology