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头颈部鳞状细胞癌多步骤起源的细胞遗传学证据。

Cytogenetic evidence of the multistep origin of head and neck squamous cell carcinomas.

作者信息

Cowan J M, Beckett M A, Ahmed-Swan S, Weichselbaum R R

机构信息

Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Ill.

出版信息

J Natl Cancer Inst. 1992 May 20;84(10):793-7. doi: 10.1093/jnci/84.10.793.

Abstract

BACKGROUND

Head and neck squamous cell carcinomas are associated with tobacco and alcohol use; therefore, the incidence of this type of tumor is expected to rise in the future as a result of the increasing numbers of female and adolescent smokers. Previous reports of cytogenetic analysis of this type of tumor have implicated a number of chromosomal regions in recurring changes, but no clear pattern of characteristic changes has emerged.

PURPOSE

We have undertaken cytogenetic analysis of 10 cell lines which were established from squamous cell carcinomas of the head and neck, to determine the possible sites of additional tumor suppressor genes and oncogenes that may contribute to malignant transformation.

METHODS

Metaphases were harvested from cultures of cells in the exponential growth phase, following exposure to Colcemid (demecolcine) at a final concentration of 30 ng/mL for 5 hours. Air-dried slides were G-banded using trypsin and Giemsa. Fifteen metaphases were photographed and fully karyotyped.

RESULTS

We observed that several chromosomal regions were lost at high frequency, including 18q (10 of 10 lines), 10p (eight of 10 lines), 3p (six of 10 lines), 8p (seven of 10 lines), and the short arms of the acrocentric chromosomes (seven of 10 lines). Nine of 10 lines had additional copies of 7p. We also noted clustering of breakpoints in a number of chromosome bands, including 1p22, 10q11.2, 11q13, and the short arms of the acrocentric chromosomes.

CONCLUSION

The observation of loss of multiple chromosomal regions in a significant number of lines analyzed is consistent with the theory that tumorigenesis occurs as the result of the accumulation of a number of genetic alterations, as proposed for colorectal carcinoma. The high frequency with which these changes are seen suggests that genes located in these regions have a role in the etiology of this type of tumor.

摘要

背景

头颈部鳞状细胞癌与吸烟和饮酒有关;因此,由于女性和青少年吸烟者数量的增加,预计未来这类肿瘤的发病率将会上升。此前关于这类肿瘤细胞遗传学分析的报告表明,一些染色体区域反复出现变化,但尚未出现明显的特征性变化模式。

目的

我们对10株源自头颈部鳞状细胞癌的细胞系进行了细胞遗传学分析,以确定可能存在的其他肿瘤抑制基因和癌基因位点,这些基因可能促成恶性转化。

方法

在指数生长期的细胞培养物中加入终浓度为30 ng/mL的秋水仙酰胺(去甲秋水仙碱)处理5小时后收获中期相。空气干燥的玻片用胰蛋白酶和吉姆萨染液进行G显带。拍摄15个中期相并进行完整的核型分析。

结果

我们观察到几个染色体区域高频缺失,包括18q(10个细胞系中的10个)、10p(10个细胞系中的8个)、3p(10个细胞系中的6个)、8p(10个细胞系中的7个)以及近端着丝粒染色体的短臂(10个细胞系中的7个)。10个细胞系中有9个有7p的额外拷贝。我们还注意到一些染色体带中存在断点聚集,包括1p22、10q11.2、11q13以及近端着丝粒染色体的短臂。

结论

在大量分析的细胞系中观察到多个染色体区域缺失,这与肿瘤发生是由多种基因改变积累所致的理论一致,这一理论也适用于结直肠癌。这些变化的高频率出现表明位于这些区域的基因在这类肿瘤的病因学中起作用。

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