Dong J T, Boyd J C, Frierson H F
Department of Pathology, University of Virginia Health System, Charlottesville, Virginia 22908-0214, USA.
Prostate. 2001 Nov 1;49(3):166-71. doi: 10.1002/pros.1131.
Loss of heterozygosity (LOH) at chromosome 13q has been frequently detected in prostate cancer, and three regions (i.e., 13q14, 13q21, and 13q33) may harbor tumor suppressor genes important in this neoplasm. In this study, we examined the frequency of 13q LOH in advanced prostate cancers, in order to determine the clinicopathologic relevance of 13q LOH.
LOH was determined by analyzing microsatellite markers in 41 cases of microdissected predominantly high grade prostate cancer tissues and their matched nonneoplastic cells. The results were compared with those generated previously for lower grade, asymptomatic cancers.
The frequencies of LOH at 13q14, 13q21, and 13q33 were 62% (21/34), 57% (20/35), and 34% (11/32), respectively. In comparison to previous results, LOH at 13q14 and 13q21 but not 13q33 was more frequent in prostate cancers that produced local clinical symptoms (bladder outlet obstruction) than those that did not (P < 0.05). LOH at 13q14 was also significantly more frequent in high grade and high stage cancers than those that were lower grade and lower stage (P < 0.05).
Although the target genes on 13q have not been identified in carcinomas of the prostate, LOH at 13q14 in particular is associated with clinically significant prostate cancers. Further fine mapping of these loci may lead to identification of tumor suppressor genes that are deleted in aggressive carcinomas of the prostate.
13号染色体长臂(13q)杂合性缺失(LOH)在前列腺癌中经常被检测到,三个区域(即13q14、13q21和13q33)可能含有对该肿瘤重要的抑癌基因。在本研究中,我们检测了晚期前列腺癌中13q LOH的频率,以确定13q LOH的临床病理相关性。
通过分析41例显微切割的主要为高级别前列腺癌组织及其匹配的非肿瘤细胞中的微卫星标记来确定LOH。将结果与先前针对低级别无症状癌症产生的结果进行比较。
13q14、13q21和13q33处的LOH频率分别为62%(21/34)、57%(20/35)和34%(11/32)。与先前结果相比,产生局部临床症状(膀胱出口梗阻)的前列腺癌中,13q14和13q21处的LOH比未产生症状的更常见(P < 0.05),而13q33处则不然。13q14处的LOH在高级别和高分期癌症中也比低级别和低分期癌症更常见(P < 0.05)。
虽然前列腺癌中13q上的靶基因尚未确定,但特别是13q14处的LOH与具有临床意义的前列腺癌相关。对这些位点的进一步精细定位可能会导致鉴定出在侵袭性前列腺癌中缺失的抑癌基因。