Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: Identification of genetic indicators that predict patient outcome
Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: Identification of genetic indicators that predict patient outcome
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DOI：
10.1111/j.1349-7006.2007.00395.x
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发表时间：
2007-03-01
期刊：
影响因子：
5.7
通讯作者：
Hirohashi, Setsuo
中科院分区：
文献类型：
--
作者：
Loukopoulos, Panayiotis;Shibata, Tatsuhiro;Hirohashi, Setsuo
我们分析了44例手术切除的胰腺腺癌的亚染色体数值畸变的阵列为基础的比较基因组杂交。不同病例间的畸变谱差异很大，表明胰腺癌存在多种或互补的进化机制，并与淋巴结转移和静脉或浆膜侵袭有关。大量以前在胰腺癌中未发现的小基因座显示出非随机的损失或增加。鉴定出1p36、4p16、7q36、9q34、11p15、11q13、14q32-33、16p13、17p11-13、17q11-25、18q21-tel、19p13、21q22和22q11-12位点的频繁缺失，以及1q25、2p16、2q21-37、3q25、5p14、5q11-13、7q21、7p22、8p22、8q21-23、10q21、12p13、13q22、15q13-22和18q11位点的频繁缺失。16个基因座重复扩增。我们发现了与一系列恶性表型显著相关的新的染色体改变。LUNX、HCK、E2F1和DNMT3b在20q11获得，p73在1p36丢失，PPM1D在17q23获得独立预测患者预后。扩增基因的表达谱鉴定Smurf1和TRRAP位于7q22.1， BCAS1位于20q13. 3 -3， VCL位于10q22.1为潜在的新型致癌基因。我们的研究结果有助于完整地描述基因组结构畸变，并确定潜在的治疗靶点和预测胰腺腺癌患者预后的遗传指标。
We analyzed the subchromosomal numerical aberrations of 44 surgically resected pancreatic adenocarcinomas by array-based comparative genomic hybridization. The aberration profile ranged widely between cases, suggesting the presence of multiple or complementary mechanisms of evolution in pancreatic cancer, and was associated with lymph node metastasis and venous or serosal invasion. A large number of small loci, previously uncharacterized in pancreatic cancer, showed non-random loss or gain. Frequent losses at 1p36, 4p16, 7q36, 9q34, 11p15, 11q13, 14q32-33, 16p13, 17p11-13, 17q11-25, 18q21-tel, 19p13, 21q22 and 22q11-12, and gains at 1q25, 2p16, 2q21-37, 3q25, 5p14, 5q11-13, 7q21, 7p22, 8p22, 8q21-23, 10q21, 12p13, 13q22, 15q13-22 and 18q11 were identified. Sixteen loci were amplified recurrently. We identified novel chromosomal alterations that were significantly associated with a range of malignant phenotypes. Gain of LUNX, HCK, E2F1 and DNMT3b at 20q11, loss of p73 at 1p36 and gain of PPM1D at 17q23 independently predicted patient outcome. Expression profiling of amplified genes identified Smurf1 and TRRAP at 7q22.1, BCAS1 at 20q13.2-3, and VCL at 10q22.1 as potential novel oncogenes. Our results contribute to a complete description of genomic structural aberrations and the identification of potential therapeutic targets and genetic indicators that predict patient outcome in pancreatic adenocarcinoma.