Allelotype of squamous cell carcinoma of the head and neck: fractional allele loss correlates with survival.
Allelotype of squamous cell carcinoma of the head and neck: fractional allele loss correlates with survival.
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DOI：
10.1038/bjc.1995.483
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发表时间：
1995-11
影响因子：
8.8
通讯作者：
Howard P
中科院分区：
文献类型：
--
作者：
Field JK;Kiaris H;Risk JM;Tsiriyotis C;Adamson R;Zoumpourlis V;Rowley H;Taylor K;Whittaker J;Howard P
等位基因不平衡或杂合性丢失(LOH)研究已被广泛用于识别染色体上可能包含假定的肿瘤抑制基因的区域。我们对80例头颈部鳞状细胞癌(SCCHN)标本进行了广泛的等位基因分型，使用了39条染色体上的145个多态微卫星标记。染色体臂3p、9p、17p和18q的等位基因频率最高，杂合率超过45%，1p、1q、2p、5q、6p、6q、8p、8q、9q、11q、13q、17q和19q的等位基因频率超过20%。将这些LOH数据与包括初治和初治肿瘤在内的一系列临床病理参数进行分析，发现9q上的LOH与病理上的淋巴结(P=0.02)相关，12q和13q上的LOH与组织病理分级相关(P=0.02)和13q上的LOH(P=0.01)。初发组3p(P=0.019)、8p(P=0.029)LOH与肿瘤部位相关，3p(P=0.019)、17p(P=0.016)LOH与肿瘤分期相关。计算了52个肿瘤的部分等位基因丢失(FAL)，发现有9个或更多染色体臂上的LOH数据的中位数为0.22(范围为0.0-0.80)。FAL和GT中位数与病理结节(P=0.01)和肿瘤分级(P=0.06)相关，提示有淋巴结转移的晚期肿瘤常有多部位LOH。FAL>；中位数与较差的存活率相关(P<；0.03)，此外，FAL>；中位数与先前未治疗的患者存活率较差相关(P<；0.019)。这些结果表明，等位基因数据提供的对遗传损伤累积的评估，为肿瘤行为和临床结果提供了一个有用的分子指标。
Allelic imbalance or loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour-suppressor genes. We have undertaken an extensive allelotype of 80 specimens of squamous cell carcinoma of the head and neck (SCCHN) using 145 polymorphic microsatellite markers on 39 chromosome arms. Allelic imbalances were found most frequently on chromosome arms 3p, 9p, 17p and 18q with over 45% LOH and imbalances on 1p, 1q, 2p, 5q, 6p, 6q, 8p, 8q, 9q, 11q, 13q, 17q and 19q were found in more than 20% of SCCHN. These LOH data were analysed against a range of clinicopathological parameters which included previously untreated and previously treated tumours; correlations were found between LOH on 9q and nodes at pathology (P = 0.02) and between histopathological grade and LOH on 12q (P = 0.02) and 13q (P = 0.01). In the group of previously untreated tumours, a correlation was found between site of tumour and LOH on 3p (P = 0.019), and 8p (P = 0.029), while TNM staging correlated with LOH on 3p (P = 0.019) and 17p (P = 0.016). Fractional allele loss (FAL) was calculated for 52 tumours with LOH data on nine or more chromosomal arms and found to have a median value of 0.22 (range 0.0-0.80). Correlations were found between FAL > median value and nodes at pathology (P = 0.01) and tumour grade (P = 0.06), demonstrating that advanced tumours with lymph node metastasis often had LOH at multiple sites. FAL > median value was found to correlate with a poor survival (P < 0.03) and, furthermore, FAL > median value correlated with poor survival in the previously untreated patients (P < 0.019). These results indicate that assessment of the accumulation of genetic damage, as provided by allelotype data, provides a useful molecular indicator of the tumour behaviour and clinical outcome.