Sabbir Md Golam, Roy Anup, Mandal Syamsundar, Dam Aniruddha, Roychoudhury Susanta, Panda Chinmay Kumar
Chittaranjan National Cancer Institute, Kolkata, India.
Int J Exp Pathol. 2006 Apr;87(2):151-61. doi: 10.1111/j.0959-9673.2006.00467.x.
Deletions in chromosome (chr.) 13q occur frequently in head and neck squamous cell carcinoma (HNSCC). Previous studies failed to identify common deleted regions in chr.13q, though several candidate tumour suppressor genes (TSGs) loci, e.g. BRCA2, RB1 and BRCAX have been localized in this chromosome, as well as no prognostic significance of the deletion has been reported. Thus, in the present study, deletion mapping of chr. 13q has been done in 55 primary HNSCC samples of Indian patients using 11 highly polymorphic microsatellite markers of which three were intragenic to BRCA2 gene, one intragenic to RB1 gene and another from BRCAX locus. The deletion in chr.13q was significantly associated with progression of HNSCC. High frequencies (27-39%) of loss of heterozygosity were found in 13q13.1 (BRCA2), 13q14.2 (RB1), 13q21.2-22.1 (BRCAX) and 13q31.1 regions. Deletions in the BRCA2 and RB1 regions were significantly correlated. The four highly deleted regions were associated with clinical stage and histological grades of the tumour as well as poor patient outcome. Deletion in the 13q31.1 region was only found to be associated with HPV infection. High frequencies (11-23%) of microsatellite size alteration (MA) were seen to overlap with the highly deleted regions. Forty per cent of the samples showed rare biallelic alteration whereas loss of normal copy of chromosome 13q was seen in five tumours. Thus, it seems that the putative TSGs located in the BRCAX and 13q31.1 regions as well as the BRCA2 and RB1 genes may have some cumulative effect in progression and poor prognosis of HNSCC. Significant association between deletion in BRCA2 and RB1 gene loci may indicate functional relationship between the genes in this tumour progression.
13号染色体（chr.）13q缺失在头颈部鳞状细胞癌（HNSCC）中频繁发生。以往的研究未能确定chr.13q上的常见缺失区域，尽管几个候选肿瘤抑制基因（TSG）位点，如BRCA2、RB1和BRCAX已定位在该染色体上，且尚未报道该缺失的预后意义。因此，在本研究中，使用11个高度多态性微卫星标记对55例印度患者的原发性HNSCC样本进行了chr. 13q缺失图谱分析，其中3个标记位于BRCA2基因内，1个位于RB1基因内，另1个来自BRCAX位点。chr.13q缺失与HNSCC进展显著相关。在13q13.1（BRCA2）、13q14.2（RB1）、13q21.2 - 22.1（BRCAX）和13q31.1区域发现了高频率（27 - 39%）杂合性缺失。BRCA2和RB1区域的缺失显著相关。这四个高度缺失区域与肿瘤的临床分期、组织学分级以及患者预后不良相关。仅发现13q31.1区域的缺失与HPV感染相关。高频率（11 - 23%）的微卫星大小改变（MA）与高度缺失区域重叠。40%的样本显示罕见的双等位基因改变，而在5个肿瘤中观察到13号染色体13q正常拷贝的缺失。因此，位于BRCAX和13q31.1区域以及BRCA2和RB1基因的假定TSG可能在HNSCC进展和预后不良中具有一些累积效应。BRCA2和RB1基因位点缺失之间的显著关联可能表明这些基因在该肿瘤进展中的功能关系。
