Phillips N J, Ziegler M R, Radford D M, Fair K L, Steinbrueck T, Xynos F P, Donis-Keller H
Department of Pathology, Saint Louis University School of Medicine, Missouri, USA.
Cancer Res. 1996 Feb 1;56(3):606-11.
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.
多个17号染色体位点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号染色体短臂上15个位点杂合性缺失检测。80%（49例中有39例）的信息性肿瘤在17p13.3区域的D17S30、D17S28或这两个位点存在等位基因缺失，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D17S28延伸至D17S30，距离为15kb。此外，一些肿瘤在D17S30探针检测到的区域内有断点。17号染色体短臂13.3区具有潜在肿瘤抑制功能的基因包括HIC-1、DPH2L（N.J.菲利普斯等人，人类二磷酸腺苷生物合成基因在17号染色体短臂13.3区的分离，待发表）/OVCA1、PEDF和CRK。HIC-1编码序列位于缺失的D17S28-S17S30区域着丝粒侧1kb处（M.马科斯·威尔士等人，《自然医学》，1:570-577，1995），但仍是一个候选基因，因为5'调控元件可能位于关键区域内。DPH2L/OVCA1编码序列的部分位于D17S28-D17S30区间内。体细胞杂交分析将PEDF定位在包括D17S28、D17S30和D17S54的区间内，而CRK被排除在该区间之外。17号染色体短臂13.3区的缺失先于TP53和BRCA1区域的缺失，因为后者的改变仅在晚期癌中出现。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例肿瘤中只有1例出现此现象。
