Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India.
Ann Surg Oncol. 2012 Jul;19 Suppl 3:S528-38. doi: 10.1245/s10434-011-1991-x. Epub 2011 Aug 23.
Alteration of chromosome 9q22.3 region is an early and frequent event in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to understand the association of candidate tumor suppressor genes PHF2, FANCC, PTCH1, and XPA located in this region in the development of HNSCC.
The alterations (deletion, promoter methylation, mutation, expression) of these genes were analyzed in 65 dysplastic head and neck lesions and 84 primary HNSCC samples. Clinicopathologic correlations were made with alterations of the genes.
Overall alterations (deletion, promoter methylation) of FANCC and PTCH1 were high in mild dysplasia and comparable in subsequent stages of tumor progression. However, PHF2 alteration was low in mild dysplasia, but increased in moderate and severe dysplasias. Alterations (deletion, promoter methylation) of FANCC and PTCH1 showed association with each other. Two novel mutations in GLI binding sites of PTCH1 promoter and a novel microsatellite marker hmPTCH1 with four alleles at immediate upstream of the gene were identified. In a case-control study, the (CGG)7 allele of hmPTCH1 was found to be susceptible for HNSCC development. Concordance was seen in the expression (RNA, protein) of these genes with their molecular alterations.
Alterations of FANCC and PTCH1 could be used as molecular marker for early diagnosis and prognosis of HNSCC.
9q22.3 染色体区域的改变是头颈部鳞状细胞癌（HNSCC）早期和频繁发生的事件。本研究旨在了解位于该区域的候选肿瘤抑制基因 PHF2、FANCC、PTCH1 和 XPA 与 HNSCC 发生发展的相关性。
分析了 65 例发育不良的头颈部病变和 84 例原发性 HNSCC 样本中这些基因的改变（缺失、启动子甲基化、突变、表达）。并与基因改变进行了临床病理相关性分析。
FANCC 和 PTCH1 的总体改变（缺失、启动子甲基化）在轻度发育不良中较高，在肿瘤进展的后续阶段相当。然而，PHF2 的改变在轻度发育不良中较低，但在中度和重度发育不良中增加。FANCC 和 PTCH1 的改变（缺失、启动子甲基化）相互关联。在 PTCH1 启动子的 GLI 结合位点发现了两个新的突变，以及一个新的微卫星标记 hmPTCH1，该标记在基因的近端上游有四个等位基因。在病例对照研究中，发现 hmPTCH1 的（CGG）7 等位基因易患 HNSCC。这些基因的表达（RNA、蛋白质）与其分子改变一致。
FANCC 和 PTCH1 的改变可用作 HNSCC 早期诊断和预后的分子标志物。
