Advances in Brief Loss of Heterozygosity Analysis Defines a Critical Region in Chromosome Ip 22 Commonly Deleted in Human Malignant Mesothelioma 1

Advances in Brief Loss of Heterozygosity Analysis Defines a Critical Region in Chromosome Ip 22 Commonly Deleted in Human Malignant Mesothelioma 1
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杂合性短暂丢失分析的进展定义了人类恶性间皮瘤 1 中常见缺失的染色体 Ip 22 的关键区域

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发表时间:
2006
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通讯作者:
J. Testa
J. Testa
中科院分区:
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作者:
Wen‐Ching Lee;B. Balsara;Zemin Liu;S. Jhanwar;J. Testa

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先前的细胞遗传学分析揭示了人类恶性间皮瘤中lp 21 -22的染色体的频繁丢失,这表明位于该位点的肿瘤抑制基因的丢失或失活可能导致间皮瘤细胞的致瘤性转化。为了更精确地定义靶基因的位置,使用短串联重复序列多态性(STRP)标记物检查了50例恶性间皮瘤的原发肿瘤标本和细胞系的杂合性丢失。选择由Cooperative Human Linkage Center建立的19个STRP标记用于1号染色体整个短臂的初步筛选。37例(74%)在Ip中至少有一个位点出现等位基因丢失。其中36例显示lp 21 -22缺失,包括23例涉及该区域的部分缺失。为了获得该区域的更高分辨率的图谱,使用来自Genethon图谱的另外13个STRP标记来定义重叠缺失的最短区域,该重叠缺失的最短区域为侧翼为基因座D1 S435和DIS 236的4-cM区段。通过核型分析和荧光原位杂交分析,证实了关键缺失区域的染色体位置在Ip 22内。
Previous cytogenetic analysis has revealed frequent losses of chromo some lp21-22 in human malignant mesothelioma, suggesting that the loss or inactivation of a tumor suppressor gene(s) residing at this site may contribute to the tumorigenic conversion of mesothelial cells. To more precisely define the location of the target gene, primary tumor specimens and cell lines from 50 malignant mesotheliomas were examined for loss of heterozygosity using short tandem repeat polymorphism (STRP) markers. Nineteen STRP markers established by the Cooperative Human Linkage Center were selected for the initial screening of the entire short arm of chromosome 1. Thirty-seven cases (74%) showed allelic losses at least at one locus in Ip. Thirty-six of these cases showed losses of lp21-22, including 23 with partial deletions involving this region. To obtain a higher resolution map of this region, another 13 STRP markers from the Genethon map were used to define the shortest region of overlapping deletions to a 4-cM segment flanked by the loci D1S435 and DIS236. The chromosomal location of the critically deleted region was confirmed to be within Ip22 by karyotypic and fluorescence in situ hybridization analyses.
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