Allelotype analysis of cervical carcinoma.
Allelotype analysis of cervical carcinoma.
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发表时间：
1994-08
期刊：
影响因子：
11.2
通讯作者：
A. B. Mitra;V. Murty;Rong G. Li;M. Pratap;U. Luthra;R. Chaganti
中科院分区：
文献类型：
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作者：
A. B. Mitra;V. Murty;Rong G. Li;M. Pratap;U. Luthra;R. Chaganti
为了确定可能在宫颈癌的发展中发挥作用的遗传事件，我们进行了详细的等位基因型分析，利用来自53个原发性肿瘤和相应的正常细胞的DNA和57个多态性探针映射到每个染色体臂，不包括短臂的近端着丝粒染色体。杂合性丢失（洛）发生在11条染色体臂上，包括1q（26%）、3p（35%）、3q（31%）、4q（46%）、5p（53%）、5q（38%）、6p（28%）、10q（28%）、11p（42%）、18p（38%）和Xq（26%）。最常见的洛位于4q（ADH 3）和5p（D5S19），提示这些染色体臂上的候选抑癌基因的丢失可能在宫颈癌的发生中起作用。在5p和Xq上鉴定的两个缺失位点代表了迄今为止在任何其他肿瘤类型中尚未报道的新的候选肿瘤抑制基因位点。人乳头状瘤病毒状态与任何显示频繁洛缺失的位点无关。采用单链构象多态性分析对17例17p缺失（TP53、D17S5或D17S28）或人乳头状瘤病毒阴性的肿瘤进行TP53突变分析。7例人乳头状瘤病毒阴性肿瘤中，有1例在D17 S28位点也显示洛缺失，其第5外显子发生突变。这项研究代表了第一次全面的遗传分析，这种癌症，并确定了几个新的功能的意义，遗传病因学的宫颈癌。
To identify the genetic events which may play a role in the development of cervical carcinoma, we performed a detailed allelotype analysis utilizing DNA from 53 primary tumors and corresponding normal cells and 57 polymorphic probes mapped to each of the chromosomal arms, excluding the short arms of the acrocentric chromosomes. Loss of heterozygosity (LOH) of > 25% was observed at sites on 11 chromosomal arms, which included 1q (26%), 3p (35%), 3q (31%), 4q (46%), 5p (53%), 5q (38%), 6p (28%), 10q (28%), 11p (42%), 18p (38%), and Xq (26%). The most frequent LOH was noted on 4q (ADH3) and 5p (D5S19), suggesting that loss of candidate tumor suppressor genes on these chromosomal arms may play a role in the development of cervical carcinoma. The two sites of deletions identified on 5p and Xq represent novel candidate tumor suppressor gene sites which have so far not been reported in any other tumor type. Human papilloma virus status did not correlate with any of the sites which showed frequent LOH. TP53 mutation analysis by single-strand conformation polymorphism analysis was performed in 17 tumors that either showed 17p deletions (TP53, D17S5, or D17S28) or were human papilloma virus negative. One of the 7 human papilloma virus-negative tumors, which also showed LOH at the D17S28 locus, had a mutation in exon 5. This study represents the first comprehensive genetic analysis of this cancer and identifies several novel features of significance to genetic etiology of cervical carcinoma.