Genome-wide analyses on loss of heterozygosity in head and neck squamous cell carcinomas
Genome-wide analyses on loss of heterozygosity in head and neck squamous cell carcinomas
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DOI：
10.1097/01.lab.0000047489.26246.e1
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发表时间：
2003-01-01
影响因子：
5
通讯作者：
Shimizu, K
中科院分区：
文献类型：
--
作者：
Beder, LB;Gunduz, M;Shimizu, K
头颈部鳞状细胞癌是一种常见的恶性肿瘤，生存率低。通过基因组研究确定肿瘤抑制基因（TSG）位点是揭示HNSCC发病机制的重要一步。因此，我们使用全基因组191个微卫星标记对22例HNSCC样本的杂合性丢失（洛）进行了综合分析。在21条染色体臂上发现53个标记具有显著的高洛（>30%）;在3 p、9 p、13 q、15 q和17 p观察到最高值，对应于D3 S2432（67%）、D9 S921-D9 S925（67%）和GATA 62 F03（86%）、D13 S1493（60%）、D15 S211（62%），和D17 S1353（88%）。在13条染色体臂中确定了15个洛丢失热点：2 q22 -23、4p15.2、4 q24 -25、5 q31、Sp23、9 p23 -24、9q31.3、9q34.2、10 q21、11 q21 -22.3、14 q11 -13、14q22.3、17 p13、18 q11和19 q12。此外，我们在HNSCC的三条染色体臂上发现了5个新的洛缺失热点，分别位于2 q33（D2 S1384）、2 q37（D2 S125）、8 q12 -13（D8 S1136）、8 q24（D8 S1128）和15 q21（D15 S211）。总之，我们全面的等位基因型分析已经揭示并证实了总共20个可能的TSG基因座，可能参与HNSCC的发展。这些结果提供了有用的线索，通过精细定位的可疑区域和随后的功能基因的分析，参与HNSCC的推定的TSGs的鉴定。
Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor survival rate. Identifying the tumor suppressor gene (TSG) loci by genomic studies is an important step to uncover the molecular mechanisms involved in HNSCC pathogenesis. We therefore performed comprehensive analyses on loss of heterozygosity (LOH) using a genome-wide panel of 191 microsatellite markers in 22 HNSCC samples. We found 53 markers with significantly high LOH (>30%) on 21 chromosomal arms; the highest values of those were observed on 3p, 9p, 13q, 15q, and 17p, corresponding to D3S2432 (67%), D9S921-D9S925 (67%) and GATA62F03 (86%), D13S1493 (60%), D15S211 (62%), and D17S1353 (88%), respectively. Fifteen hot spots of LOH were defined in 13 chromosomal arms: 2q22-23, 4p15.2, 4q24-25, 5q31, Sp23, 9p23-24, 9q31.3, 9q34.2, 10q21, 11q21-22.3, 14q11-13, 14q22.3, 17p13, 18q11, and 19q12 as loci reported previously in HNSCCs. Furthermore, we identified five novel hot spots of LOH on three chromosomal arms in HNSCC at 2q33 (D2S1384), 2q37 (D2S125), 8q12-13 (D8S1136), 8q24 (D8S1128), and 15q21 (D15S211). In conclusion, our comprehensive allelotype analyses have unveiled and confirmed a total of 20 possible TSG loci that could be involved in the development of HNSCC. These results provide useful clues for identification of putative TSGs involved in HNSCC by fine mapping of the suspected regions and subsequent analysis for functional genes.