Frequent deletion of ING2 locus at 4q35.1 associates with advanced tumor stage in head and neck squamous cell carcinoma
Frequent deletion of ING2 locus at 4q35.1 associates with advanced tumor stage in head and neck squamous cell carcinoma
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DOI：
10.1007/s00432-008-0507-y
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发表时间：
2009-05-01
影响因子：
3.6
通讯作者：
Nagai, Noriyuki
中科院分区：
文献类型：
--
作者：
Borkosky, Silvia S.;Gunduz, Mehmet;Nagai, Noriyuki
背景ING家族成员的杂合性丢失（洛）在头颈部鳞状细胞癌（HNSCC）中已被证实，但ING 2除外。ING2基因定位于染色体4q35.1，与ING家族其他成员一样，是一个很有前途的抑癌基因。在这项研究中，我们进行洛分析ING2在HNSCC.Materials和方法，我们进行了洛分析，从80对正常和HNSCC组织的DNA，使用一个专门设计的微卫星标记染色体4q35.1，检测等位基因丢失ING2。在68例样本中进行了TP53突变分析及其与ING2染色体缺失的关系。采用统计学方法分析洛缺失状态与临床病理特征的相关性。结果55例患者中有30例（54.6%）存在洛缺失（LOH）。洛缺失与肿瘤T分期、放疗和化疗的应用有统计学意义（P = 0.02）。淋巴结阳性状态（N）是影响OS（P = 0.031）和DFS（P = 0.044）的唯一独立预后因素。高百分比的洛缺失提示ING2是HNSCC中的候选TSG。高洛缺失频率与晚期T分期相关，提示ING2洛缺失可能发生在晚期。
Background Loss of heterozygosity (LOH) in the ING family members has been shown in head and neck squamous cell carcinoma (HNSCC) except for ING2. Like all the other members of ING family, ING2, which is located at chromosome 4q35.1, is a promising tumor suppressor gene (TSG). In this study, we performed LOH analysis of ING2 in HNSCC and compared it with clinicopathological variables.Materials and methods We performed LOH analysis in DNAs from 80 paired of normal and HNSCC tissues, using a specifically designed microsatellite marker on chromosome 4q35.1, which detects allelic loss of ING2. TP53 mutation analysis and its relationship with ING2 chromosomal deletion were also performed in available 68 of the samples. The correlation between LOH status and clinicopathological characteristics was evaluated by using statistical methods. The overall survival (OS) and disease free survival (DFS) were also determined.Results LOH was detected in 54.6% (30/55) of the informative samples. Statistical significance was obtained between LOH and tumor (T) stage (P = 0.02), application of radiotherapy and chemotherapy. Positive node status (N) appeared to be the only independent prognostic factor for both OS (P = 0.031) and DFS (P = 0.044).Conclusions Our study showed allelic loss of 4q35.1 in HNSCC. The high percentage of LOH suggests ING2 as a candidate TSG in HNSCC. High LOH frequency was statistically associated with advanced T stage, suggesting that ING2 LOH might occur in late stages during HNSCC progression.