Loss of heterozygosity at the short arm of chromosome 3 in microdissected cervical intraepithelial neoplasia
Loss of heterozygosity at the short arm of chromosome 3 in microdissected cervical intraepithelial neoplasia
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DOI：
10.1016/s0304-3835(00)00398-0
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发表时间：
2000-06-30
期刊：
影响因子：
9.7
通讯作者：
Wong, YF
中科院分区：
文献类型：
--
作者：
Chung, TKH;Cheung, TH;Wong, YF
杂合性缺失（LOH）是许多人类肿瘤中常见的遗传发现，包括宫颈癌。在宫颈癌前体，宫颈上皮内瘤变（CIN）的特定位点检测LOH可能有助于阐明这种具有明确定义的组织学癌前期的癌症的演变。然而，分子遗传学研究CIN是困难的，因为许多病变非常小，有时不明确的地形。采用引物延伸预扩增（PEP）全基因组扩增与显微解剖相结合的方法，分析了CINs染色体3p上18个多态微卫星重复序列。这些标记包括染色体区域3pter-3p12。15例低级别CIN （CIN 1）中有5例（33%）检测到一个或多个位点的LON，而24例高级别CIN （CIN 2和3）中有22例（92%）检测到LON （P < 0.01）。LOH发生率最高的位点为D3S1038 (3p26.1-3p25.2)，为41%。在其他位点也发现了频繁的LOH（超过20%），包括D3S1110 (3p35.3-3p25.1) (31%), D3S656 (3p25.1) (24%), D3S1076 (3p21.2-3p21.1) (29%), D3S1300 (3p21.1-3p14.2) (24%), D3S1600 (3p14.2-3p14.1)（24%）和D3S1079 (3p13)（25%）。本研究和其他研究结果表明，染色体3p的遗传改变在高级别CIN中很常见，可能是宫颈癌发生的早期事件。在宫颈肿瘤中起作用的肿瘤抑制基因可能位于3号染色体短臂上，可能位于或靠近3p26.1-25.1、3p21.2-21.1和3p14.2-13。(C) 2000爱思唯尔科学爱尔兰有限公司版权所有
Loss of heterozygosity (LOH) is a common genetic finding in many human neoplasms, including cervical cancer. The detection of LOH at specific loci in the precursor of cervical cancer, cervical intraepithelial neoplasia (CIN) may help in elucidating the evolution of this cancer, which has a clearly defined histological premalignant phase. However, molecular genetic investigation of CIN is difficult because many of the lesions are very small and sometimes ill defined topographically. In this study we analyzed eighteen polymorphic microsatellite repeats on chromosome 3p in CINs using a method of primer extension pre-amplification (PEP) for whole genome amplification combined with microdissection. These markers encompass chromosome region 3pter-3p12. LON at one or more loci was detected in five (33%) out of the 15 informative cases with low grade CIN (CIN 1), while 22 (92%) out of 24 cases with high grade CIN (CIN 2 and 3) (P < 0.01). The highest incidence (41%) of LOH was detected at locus D3S1038 (3p26.1-3p25.2). Frequent LOH (more than 20%) was also found at other loci including D3S1110 (3p35.3-3p25.1) (31%), D3S656 (3p25.1) (24%), D3S1076 (3p21.2-3p21.1) (29%), D3S1300 (3p21.1-3p14.2) (24%), D3S1600 (3p14.2-3p14.1) (24%), and D3S1079 (3p13) (25%). The results from this study taken together with others indicate that the genetic alterations on chromosome 3p are common in high grade of CIN and are probably early events in cervical carcinogenesis. Tumor suppressor gene(s) that play a role in cervical neoplasm may be located on the short arm of chromosome 3, likely at or near 3p26.1-25.1, 3p21.2-21.1, and 3p14.2-13. (C) 2000 Elsevier Science Ireland Ltd, All rights reserved.