Allelic deletion on chromosome 17p13.3 in early ovarian cancer.
Allelic deletion on chromosome 17p13.3 in early ovarian cancer.
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发表时间：
1996-02
期刊：
影响因子：
11.2
通讯作者：
N. Phillips;Michelle Ziegler;D. Radford;K. Fair;T. Steinbrueck;F. Xynos;H. Donis-Keller
中科院分区：
文献类型：
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作者：
N. Phillips;Michelle Ziegler;D. Radford;K. Fair;T. Steinbrueck;F. Xynos;H. Donis-Keller
多个17号染色体基因座可能参与卵巢癌的发生。对57例散发性卵巢上皮性肿瘤进行了17号染色体上15个位点的杂合性缺失检测。80%（49例中的39例）的信息性肿瘤在17p13.3的D17 S30、D17 S28或该区域内的这两个位点处有等位基因丢失，包括7例低恶性潜能肿瘤中的3例和5例非转移性癌中的4例。重叠缺失的最小区域从D17 S28延伸到D17 S30，距离为15 kb。此外，几种肿瘤在D17 S30探针检测到的区域内具有断点。染色体17p13.3可能具有抑癌功能的基因包括HIC-1、DPH 2L（N. J.菲利普斯等人，染色体17 p13.3上的人二苯二甲酰胺生物合成基因的分离，提交出版）/OVCA 1、PEDF和CRK。HIC-1编码序列位于D17 S28-S17 S30缺失区的1 kb处（M. Makos Wales等人，Nat. Med.，1：570-577，1995），但仍然是候选者，因为5 '-调控元件可能位于关键区域内。部分DPH 2L/OVCA 1编码序列位于D17 S28-D17 S30区间内。体细胞杂种分析将PEDF置于包括D17 S28、D17 S30和D17 S54的区间中，而CRK被排除在该区间之外。染色体17p13.3缺失先于TP 53和BRCA 1区域缺失，因为后者的变化仅见于高分期癌。微卫星不稳定性在散发性卵巢癌发生中仅起次要作用，因为57例肿瘤中仅1例显示此发现。
Multiple chromosome 17 loci may be involved in ovarian carcinogenesis. Fifty-seven sporadic ovarian epithelial tumors were examined for loss of heterozygosity at 15 loci on chromosomes 17p. Eighty % (39 of 49) of informative tumors had allelic loss in 17p13.3 at D17S30, D17S28, or both loci within this region, including 3 of 7 tumors of low malignant potential and 4 of 5 nonmetastatic carcinomas. The smallest region of overlapping deletions extends from D17S28 to D17S30, a distance of 15 kb. Furthermore, several tumors have breakpoints within the region detected by the D17S30 probe. Chromosome 17p13.3 genes with potential tumor suppressor function include HIC-1, DPH2L (N. J. Phillips et al. Isolation of a human diphthamide biosynthesis gene on chromosome 17p13.3, submitted for publication)/OVCA1, PEDF, and CRK. The HIC-1 coding sequence lies i kb centromeric to the D17S28-S17S30 region of deletion (M. Makos Wales et al., Nat. Med., 1:570-577, 1995) but remains a candidate because 5'-regulatory elements may lie within the critical region. Portions of the DPH2L/OVCA1 coding sequence lie within the D17S28-D17S30 interval. Somatic cell hybrid analysis places PEDF in an interval including D17S28, D17S30, and D17S54, whereas CRK is excluded from this interval. Chromosome 17p13.3 loss precedes TP53 and BRCA1 region deletions because the latter changes are see only in high-stage carcinomas. Microsatellite instability plays only a minor role in sporadic ovarian carcinogenesis because only 1 of 57 tumors showed this finding.