Genome-wide semiquantitative microsatellite analysis of human hepatocellular carcinoma: discrete mapping of smallest region of overlap of recurrent chromosomal gains and losses

Genome-wide semiquantitative microsatellite analysis of human hepatocellular carcinoma: discrete mapping of smallest region of overlap of recurrent chromosomal gains and losses
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DOI:
10.1016/j.cancergencyto.2005.09.002
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发表时间:
2006-05-01
影响因子:
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通讯作者:
Nakao, Kazuwa
Nakao, Kazuwa
中科院分区:
其他
文献类型:
--
作者:
Nishimura, Takafumi;Nishida, Naoshi;Nakao, Kazuwa

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复发性染色体在1q、6p、8q和17q处增加,或在1p、4q、6q、8p、9p、13q、16q和17p处丢失是人类肝细胞癌(HCC)的常见特征。为了精确确定最短重叠区(SRO),在手术或尸检时获得的49例HCC进行了全面的微卫星分析,使用分布在22个常染色体和X染色体中几乎相等距离的400个标记。每个显示不平衡的等位基因都受到比较双链聚合酶链反应的影响,使用保留的等位基因作为内部控制,以确定不平衡是染色体获得还是丢失的结果。测定了以下复发性染色体得失的SRO: -1p36.22-p36.33, D1S450-D1S2893, 5.0兆碱基对(Mbp), + 1q23.3-q25.3,与D1S2619相似的D1S2878, 16.9 Mbp;-4q21.2类似于q24, D4S2964-D4S1572, 23.0 Mbp;-6q23.3类似于qter, D6S292-qter, 34.7 Mb;-8p22类似于p23.1, M549-MS550, 4.8 Mbp- +8q12.2-q24.13, MS260-MS514, 61.8 Mbp: -13q13.3-q22.1, D13S218-D13S156, 35.6 Mbp: -16q22.1类似于qter, D16S503-qter, 26.7 Mbp;和-17p12类似于pter, D17S921-pter, 14.2 Mbp。与我们最初的预期相反,许多HCC显示染色体臂的主要缺失或增加,因此许多基因被包括在SRO中。虽然在这些SRO中定位的一些推定的癌基因或肿瘤抑制基因可能是重要的,但许多其他基因的相对拷贝数变化可能影响HCC的发病机制。(c) 2006爱思唯尔公司版权所有。
Recurrent chromosomal gains at 1q, 6p, 8q, and 17q, or losses at 1p, 4q, 6q, 8p, 9p, 13q, 16q, and 17p are common features of human hepatocellular carcinoma (HCC). For precise determination of the shortest region of overlap (SRO), 49 HCC obtained at the time of surgery or autopsy were subjected to comprehensive microsatellite analysis by using 400 markers distributed at almost equal distances throughout the 22 autosomes and X chromosomes. Each allele showing imbalance was subjected to comparative duplex polymerase chain reaction using a retained allele as an internal control to determine whether the imbalance was the result of chromosomal gain or loss. The following SRO of recurrent chromosomal gains and losses were determined: -1p36.22-p36.33, D1S450-D1S2893, 5.0 mega-base pairs (Mbp), + 1q23.3-q25.3, D1S2878 similar to D1S2619, 16.9 Mbp; -4q21.2 similar to q24, D4S2964-D4S1572, 23.0 Mbp; -6q23.3 similar to qter, D6S292-qter, 34.7 Mb; -8p22 similar to p23.1, M549-MS550, 4.8 Mbp- +8q12.2-q24.13, MS260-MS514, 61.8 Mbp: -13q13.3-q22.1, D13S218-D13S156, 35.6 Mbp: -16q22.1 similar to qter, D16S503-qter, 26.7 Mbp; and -17p12 similar to pter, D17S921-pter, 14.2 Mbp. Contrary to our initial expectations, many HCC showed major deletions or additions of chromosome arms, so that a number of genes were included in the SRO. Although some putative oncogenes or tumor suppressor genes mapped in these SRO may be important, relative copy number changes of numerous other genes may affect pathogenesis of HCC. (c) 2006 Elsevier Inc. All rights reserved.