Huang H, Reed C P, Mordi A, Lomberk G, Wang L, Shridhar V, Hartmann L, Jenkins R, Smith D I
Department of Laboratory Medicine and Pathology, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
Genes Chromosomes Cancer. 1999 Jan;24(1):48-55.
We previously showed that FRA7G, an aphidicolin-inducible common fragile site at 7q31.2, colocalized with the common region of loss of heterozygosity (LOH) in a number of different tumors. Based on the sequence analysis of 150 Kb in the FRA7G region, we identified four new polymorphic microsatellite markers. In this article, we have used these four microsatellite markers and eight additional markers from 7q22-32 to analyze the breakage and loss of the region surrounding FRA7G in 49 invasive epithelial ovarian cancers and three borderline ovarian tumors. No allelic loss was detected in the ovarian tumors of borderline malignancy, but 71% (35/49) of the invasive tumors showed LOH at one or more loci in the region analyzed. Of the 12 markers analyzed, most of the markers exhibiting a high frequency of LOH were within FRA7G, and the highest frequency of LOH was seen with the new marker 7G14 (37%, 15/41). Breakpoint analysis in tumors with LOH demonstrated that the frequent loss of DNA sequences seen within the FRA7G region was due to frequent small interstitial deletions and not a result of loss of the whole fragile site region. These findings indicate that FRA7G does play a role in the breakage and loss of 7q sequences in invasive ovarian cancer. In addition, the newly identified markers enable us to further delineate a smallest common region of loss in invasive ovarian tumors to a 150-Kb region flanked by markers D7S486 and 7G14.
我们之前的研究表明,FRA7G是位于7q31.2的一种阿非科林诱导型常见脆性位点,在许多不同肿瘤中与杂合性缺失(LOH)的共同区域共定位。基于对FRA7G区域150 Kb的序列分析,我们鉴定出四个新的多态性微卫星标记。在本文中,我们使用这四个微卫星标记以及另外八个来自7q22 - 32的标记,分析了49例浸润性上皮性卵巢癌和3例交界性卵巢肿瘤中FRA7G周围区域的断裂和缺失情况。在交界性恶性卵巢肿瘤中未检测到等位基因缺失,但71%(35/49)的浸润性肿瘤在分析区域的一个或多个位点显示出LOH。在所分析的12个标记中,大多数显示高频率LOH的标记位于FRA7G内,新标记7G14的LOH频率最高(37%,15/41)。对有LOH的肿瘤进行断点分析表明,FRA7G区域内常见的DNA序列缺失是由于频繁的小间隙缺失,而非整个脆性位点区域的丢失。这些发现表明FRA7G在浸润性卵巢癌中7q序列的断裂和缺失中确实起作用。此外,新鉴定的标记使我们能够将浸润性卵巢肿瘤中最小的共同缺失区域进一步划定为一个150 Kb的区域,两侧分别为标记D7S486和7G14。