Hyytinen Eija-Riitta, Saadut Rega, Chen Ceshi, Paull Lindsay, Koivisto Pasi A, Vessella Robert L, Frierson Henry F, Dong Jin-Tang
Department of Pathology, University of Virginia Health System, Charlottesville, VA 22908-0214, USA.
Genes Chromosomes Cancer. 2002 Jul;34(3):306-12. doi: 10.1002/gcc.10065.
Deletion of the long arm of chromosome 6 (6q) frequently occurs in many neoplasms, including carcinomas of the prostate and breast and melanoma, suggesting the location of a tumor-suppressor gene or genes at 6q. At present, however, the region of deletion has not been well defined, and the target gene of deletion remains to be identified. In this study, we analyzed 44 primary prostate cancers with 16 polymorphic markers for loss of heterozygosity (LOH) by using PCR-based techniques. We also examined 23 cell lines/xenografts of prostate cancer with 38 markers for LOH by the method of homozygosity mapping of deletion. LOH at 6q16 - q22 was detected in 21 of 44 (48%) primary tumors and in 12 of 23 (52%) cell lines/xenografts. Two regions of LOH were defined. One was 7.5 cM at 6q16 - q21 between markers D6S1716 and D6S1580, and the other was 4.3 cM at 6q22 between D6S261 and D6S1702. Whereas no correlation was found between LOH at 6q16-q22 and patient age at diagnosis or Gleason score, tumors at higher stage appear to have more frequent LOH. These findings suggest that deletion of 6q16 - q22 is a frequent event in prostate cancer, and that the deletion originates from two distinct regions. These results should be useful in identifying the target gene(s) of deletion at 6q.
6号染色体长臂(6q)的缺失在许多肿瘤中经常发生,包括前列腺癌、乳腺癌和黑色素瘤,这表明6q区域存在一个或多个肿瘤抑制基因。然而,目前缺失区域尚未明确界定,缺失的靶基因仍有待确定。在本研究中,我们使用基于PCR的技术,分析了44例原发性前列腺癌中16个多态性标记的杂合性缺失(LOH)。我们还通过缺失纯合性定位的方法,检测了23个前列腺癌细胞系/异种移植瘤中的38个标记的LOH。在44例原发性肿瘤中的21例(48%)以及23个细胞系/异种移植瘤中的12例(52%)检测到6q16 - q22处的LOH。确定了两个LOH区域。一个位于6q16 - q21,标记D6S1716和D6S1580之间,长度为7.5 cM;另一个位于6q22,D6S261和D6S1702之间,长度为4.3 cM。虽然在6q16 - q22处的LOH与患者诊断时的年龄或Gleason评分之间未发现相关性,但较高分期的肿瘤似乎有更频繁的LOH。这些发现表明,6q16 - q22的缺失在前列腺癌中是一个常见事件,且该缺失起源于两个不同区域。这些结果将有助于确定6q缺失的靶基因。