LIMD1 is more frequently altered than RB1 in head and neck squamous cell carcinoma: clinical and prognostic implications.
LIMD1 is more frequently altered than RB1 in head and neck squamous cell carcinoma: clinical and prognostic implications.
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DOI：
10.1186/1476-4598-9-58
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发表时间：
2010-03-12
期刊：
影响因子：
37.3
通讯作者：
Panda CK
中科院分区：
文献类型：
--
作者：
Ghosh S;Ghosh A;Maiti GP;Mukherjee N;Dutta S;Roy A;Roychoudhury S;Panda CK
为了解两个相互作用的蛋白LIMD1和pRb在头颈部鳞状细胞癌(HNSCC)发生发展中的作用，我们分析了25例头颈部发育不良病变、58例HNSCC原发灶和两个HNSCC细胞系中这两个基因的变化。分析LIMD1和RB1的缺失以及LIMD1的突变和启动子甲基化分析。对LIMD1连锁的微卫星标记hmlimD1进行基因分型，找出易感等位基因。用定量聚合酶链式反应(Q-PCR)分析LIMD 1和RB1的mRNA表达。采用免疫组织化学方法检测RB1蛋白的表达。这些基因的改变与不同的临床病理参数有关。在所研究的样本中观察到高频率的LIMD1改变[94%(78/83)]。与频繁缺失和甲基化相比，LIMD1DNA突变在肿瘤进展过程中明显增加(P=0.007)。在LIMD1中发现了6个新的外显子1突变和1个新的内含子4/外显子5剪接连接突变，以及一个易感的hmlimD1(CA)20等位基因。其中一些突变[42%(14/33)]产生了不起作用的蛋白质。Rb1缺失罕见(27%)。LIMD1mRNA表达水平(25.1±19.04)显著低于RB1(3.8±8.09)，与其分子水平变化相一致。PRB表达式支持该数据。在未感染HPV的烟草成瘾患者中，LIMD1改变的肿瘤预后较差。这些基因的共同改变导致了更糟糕的患者结果。我们的研究提示LIMD1失活是HNSCC发生的主要事件，而不是RB1失活。
To understand the role of two interacting proteins LIMD1 and pRB in development of head and neck squamous cell carcinoma (HNSCC), alterations of these genes were analyzed in 25 dysplastic head and neck lesions, 58 primary HNSCC samples and two HNSCC cell lines. Deletions of LIMD1 and RB1 were analyzed along with mutation and promoter methylation analysis of LIMD1. The genotyping of LIMD1 linked microsatellite marker, hmlimD1, was done to find out any risk allele. The mRNA expression of LIMD1 and RB1 were analyzed by Q-PCR. Immunohistochemical analysis of RB1 was performed. Alterations of these genes were correlated with different clinicopathological parameters. High frequency [94% (78/83)] of LIMD1 alterations was observed in the samples studied. Compare to frequent deletion and methylation, mutation of LIMD1 was increased during tumor progression (P = 0.007). Six novel mutations in exon1 and one novel intron4/exon5 splice-junction mutation were detected in LIMD1 along with a susceptible hmlimD1 (CA)20 allele. Some of these mutations [42% (14/33)] produced non-functional proteins. RB1 deletion was infrequent (27%). Highly reduced mRNA expression of LIMD1 (25.1 ± 19.04) was seen than RB1 (3.8 ± 8.09), concordant to their molecular alterations. The pRB expression supported this data. Tumors with LIMD1 alterations in tobacco addicted patients without HPV infection showed poor prognosis. Co-alterations of these genes led the worse patients' outcome. Our study suggests LIMD1 inactivation as primary event than inactivation of RB1 in HNSCC development.
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影响因子：
11.5
作者：
Perrone, Federica;Suardi, Simona;Pilotti, Silvana
通讯作者：
Pilotti, Silvana
影响因子：
2.6
作者：
Koch, WM;Lango, M;Sidransky, D
通讯作者：
Sidransky, D
影响因子：
1.7
作者：
Edwards, MJ;Thomas, RC;Wong, YL
通讯作者：
Wong, YL
DOI：
10.1073/pnas.0805003105
发表时间：
2008-12-16
影响因子：
11.1
作者：
Sharp, Tyson V.;Al-Attar, Ahmad;Longmore, Gregory D.
通讯作者：
Longmore, Gregory D.
影响因子：
8
作者：
Wang, BS;Ren, JW;Lee, CGL
通讯作者：
Lee, CGL