Shridhar V, Staub J, Huntley B, Cliby W, Jenkins R, Pass H I, Hartmann L, Smith D I
Department of Experimental Pathology and Laboratory Medicine, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
Oncogene. 1999 Jul 1;18(26):3913-8. doi: 10.1038/sj.onc.1202756.
Detailed deletion mapping of chromosome 6q sequences in invasive ovarian tumors have implicated several broad regions involving 6q14-16, 6q21-23, 6q25-26, and the telomeric portion in band 6q27 as regions of frequent loss in this malignancy. In order to define regions of loss involved in the development of ovarian cancer, we used 23 polymorphic markers on 6q to examine allelic loss in 25 high-grade, late stage ovarian tumors. Four non-overlapping deletion regions were observed: (1) at 6q21-22.3 (D6S301-D6S292); (2) within a 1 cM region at 23.2-23.3 between markers D6S978-D6S1637 (at D6S311); (3) at 6q26 (between markers D6S411-D6S1277) and (4) at 6q27 with the markers D6S297 and D6S193. The highest region of loss was observed with marker D6S311 (lost in 17 of 19 informative cases, 89%) in 6q23.3, followed by D6S977 and D6S1637 (71 and 55%, respectively). The average fractional allele loss in the high-grade tumors was around 35%. Previous reports have shown 6q27 as the region of most frequent loss in invasive ovarian cancer. However, our results indicate a novel region in 6q23.3 (spanning less than 500 Kb distance between the markers) with the highest loss, implicating this region of chromosome 6q to harbor a putative tumor suppressor gene involved in the development of invasive epithelial ovarian cancer.
对侵袭性卵巢肿瘤中6号染色体q臂序列进行的详细缺失图谱分析表明,有几个广泛区域涉及6q14 - 16、6q21 - 23、6q25 - 26以及6q27带的端粒部分,这些区域在这种恶性肿瘤中经常发生缺失。为了确定与卵巢癌发生相关的缺失区域,我们使用了6号染色体q臂上的23个多态性标记,来检测25例高级别晚期卵巢肿瘤中的等位基因缺失情况。观察到四个非重叠的缺失区域:(1)位于6q21 - 22.3(D6S301 - D6S292);(2)在标记D6S978 - D6S1637之间(在D6S311处)23.2 - 23.3的1厘摩区域内;(3)位于6q26(标记D6S411 - D6S1277之间)以及(4)位于6q27,带有标记D6S297和D6S193。在6q23.3处,标记D6S311观察到的缺失率最高(19例信息性病例中有17例缺失,占89%),其次是D6S977和D6S1637(分别为71%和55%)。高级别肿瘤中等位基因的平均缺失率约为35%。先前的报道显示6q27是侵袭性卵巢癌中最常发生缺失的区域。然而,我们的结果表明在6q23.3处有一个新的区域(标记之间跨度小于500千碱基对)缺失率最高,这意味着6号染色体q臂的这个区域含有一个与侵袭性上皮性卵巢癌发生相关的假定肿瘤抑制基因。