Deletion at 13q21 is associated with aggressive prostate cancers.

Deletion at 13q21 is associated with aggressive prostate cancers.
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DOI:
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发表时间:
2000-07
期刊:
影响因子:
11.2
通讯作者:
J. Dong;Ceshi Chen;B. Stultz;J. Isaacs;H. Frierson
J. Dong;Ceshi Chen;B. Stultz;J. Isaacs;H. Frierson
中科院分区:
医学1区
文献类型:
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作者:
J. Dong;Ceshi Chen;B. Stultz;J. Isaacs;H. Frierson

文献摘要

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先前的细胞遗传学和分子遗传学分析表明,13号染色体q21带携带一个与前列腺癌发生有关的肿瘤抑制基因。然而,确切的基因位置尚未确定。在这项研究中,我们研究了前列腺癌标本和细胞系/异种移植物在13 q21的基因缺失,使用组织显微切割和双重PCR的方法。在147例前列腺癌样本中有13例(9%)检测到13 q21缺失。在前列腺癌的LNCaP细胞系和PC-82异种移植物中也检测到相同区域的缺失。LNCaP和PC-82中缺失的重叠区域跨越3.1 cM或2.9 cR,其相当于1-3 Mb。内皮素受体B基因(可能是位于13 q21的抑癌基因)不在缺失区域。在13例13 q21缺失的前列腺肿瘤中,5例为转移瘤,7例为原发性低分化肿瘤。唯一的原发性肿瘤,不是低分化,但有删除发生在一个最年轻的患者(49岁)在诊断。这些结果提供了证据,13 q21可能含有一个未知的基因,其失活发生在一些侵袭性前列腺癌。此外,本研究为13 q21基因的克隆和鉴定提供了一个框架。
Previous cytogenetic and molecular genetic analyses suggest that the q21 band of chromosome 13 harbors a tumor suppressor gene(s) involved in prostatic carcinogenesis. The precise genetic location, however, has not been defined. In this study, we examined prostate cancer specimens and cell lines/xenograft for genetic deletions at 13q21, using the methods of tissue microdissection and duplex PCR. Deletions at 13q21 were detected in 13 of 147 (9%) prostate cancer samples. Deletion of the same region was also detected in the LNCaP cell line and the PC-82 xenograft of prostate cancer. The overlapping region of deletion in LNCaP and PC-82 spans 3.1 cM or 2.9 cR, which is equivalent to 1-3 Mb. The endothelin receptor B gene, a possible tumor suppressor gene at 13q21, was not located in the region of deletion. Among the 13 prostate neoplasms with deletion at 13q21, 5 were metastases, and 7 were poorly differentiated primary tumors. The only primary tumor that was not poorly differentiated but had deletion occurred in one of the youngest patients (49 years) at diagnosis. These results provide evidence that 13q21 may harbor an unidentified gene(s) whose inactivation occurs in some aggressive carcinomas of the prostate. In addition, this study provides a framework for the cloning and identification of the 13q21 gene(s).