Chang Bao-Li, Liu Wennuan, Sun Jishan, Dimitrov Latchezar, Li Tao, Turner Aubrey R, Zheng Siqun L, Isaacs William B, Xu Jianfeng
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Cancer Res. 2007 May 1;67(9):4098-103. doi: 10.1158/0008-5472.CAN-06-4570.
The evidence for tumor suppressor genes at 8p is well supported by many somatic deletion studies and genetic linkage studies. However, it remains a challenge to pinpoint the tumor suppressor genes at 8p primarily because the implicated regions are broad. In this study, we attempted to narrow down the implicated regions by incorporating evidence from both somatic and germline studies. Using high-resolution Affymetrix arrays, we identified two small common deleted regions among 55 prostate tumors at 8p23.1 (9.8-11.5 Mb) and 8p21.3 (20.6-23.7 Mb). Interestingly, our fine mapping linkage analysis at 8p among 206 hereditary prostate cancer families also provided evidence for linkage at these two regions at 8p23.1 (5.8-11.2 Mb) and at 8p21.3 (19.6-23.9 Mb). More importantly, by combining the results from the somatic deletion analysis and genetic linkage analysis, we were able to further narrow the regions to approximately 1.4 Mb at 8p23.1 and approximately 3.1 Mb at 8p21.3. These smaller consensus regions may facilitate a more effective search for prostate cancer genes at 8p.
许多体细胞缺失研究和基因连锁研究都有力地支持了8p上存在肿瘤抑制基因的证据。然而，要精确确定8p上的肿瘤抑制基因仍然是一项挑战，主要原因是涉及的区域很宽泛。在本研究中，我们试图通过整合体细胞和种系研究的证据来缩小涉及的区域。使用高分辨率的Affymetrix芯片，我们在55例前列腺肿瘤中确定了8p23.1（9.8 - 11.5 Mb）和8p21.3（20.6 - 23.7 Mb）两个小的常见缺失区域。有趣的是，我们在206个遗传性前列腺癌家族中对8p进行的精细定位连锁分析也为8p23.1（5.8 - 11.2 Mb）和8p21.3（19.6 - 23.9 Mb）这两个区域的连锁提供了证据。更重要的是，通过结合体细胞缺失分析和基因连锁分析的结果，我们能够将8p23.1的区域进一步缩小到约1.4 Mb，将8p21.3的区域缩小到约3.1 Mb。这些更小的共识区域可能有助于更有效地寻找8p上的前列腺癌基因。
