Fine deletion analysis of 1p36 chromosomal region in oral squamous cell carcinomas
Fine deletion analysis of 1p36 chromosomal region in oral squamous cell carcinomas
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DOI：
10.1111/j.1600-0714.2008.00666.x
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Nagai, Noriyuki
中科院分区：
文献类型：
--
作者：
Lefeuvre, Mathieu;Gunduz, Mehmet;Nagai, Noriyuki
鳞状细胞癌是口腔最常见的癌症类型，约50%的患者死于这种疾病。不幸的是，人们对口腔鳞状细胞癌(OSCC)形成的分子机制知之甚少。最近，有报道称，在各种类型的癌症中，1p36染色体区域缺失，并被怀疑含有各种肿瘤抑制基因(TSG)。为探讨口腔鳞癌易感基因S在1p36区域的易感区域，采用9个微卫星标记对27例口腔鳞癌患者的正常组织和肿瘤组织进行杂合性丢失(LOH)分析，发现85%的病例(23/27)至少有一个基因座存在LOH。有趣的是，在所分析的27个病例中，也有7%(2个)发现了微卫星不稳定性。D1S243(25%)、D1S468(22%)、D1S450(25%)、D1S228(38%)、D1S199(28%)和D1S1676(23%)等标记具有较高的杂合性缺失频率，在口腔鳞癌中发现了3个优先缺失的区域：区域1(D1S468-D1S243)、区域2(D1S450-D1S228)和区域3(D1S199-D1S1676)。多个候选TSG，如RIZ1、p73、UBE4B、Rap1GAP、EPHB2和RUNX3，位于这三个区域。本研究获得的数据可用于进一步分析这些与口腔鳞癌发生有关的基因的功能。
Squamous cell carcinoma is the most common cancer type of the oral cavity and approximately 50% of the patients succumb to the disease. Unfortunately, few are known about the molecular mechanisms involving in the formation of oral squamous cell carcinoma (OSCC). Recently, it has been reported that 1p36 chromosomal region is deleted in various cancer types and is suspected to harbor various tumor suppressor genes (TSGs). However, limited studies exist on genetics alteration on 1p36 in OSCC and the responsible TSG remained unidentified.To investigate area susceptible to harbor TSG(s) involved in OSCC on 1p36 region, paired normal and tumor tissues of 27 patients with diagnosis of OSCC have been analyzed for loss of heterozygosity (LOH) using nine microsatellite markers based on recent gene mapping.LOH was found at least in one locus in 85% of the cases (23 of 27). Interestingly, microsatellite instability was also found in 7% (two of 27) of the cases analyzed. The higher LOH frequencies were found with the markers D1S243 (25%), D1S468 (22%), D1S450 (25%), D1S228 (38%), D1S199 (28%), and D1S1676 (23%).Three preferentially deleted regions have been identified in OSCC: region 1 (D1S468-D1S243), region 2 (D1S450-D1S228), and region 3 (D1S199-D1S1676). Multiple candidate TSGs, such as RIZ1, p73, UBE4B, Rap1GAP, EPHB2, and RUNX3, are located in these three areas. The data obtained in this study can be used for further functional analysis of these genes involved in OSCC carcinogenesis.