Microsatellite instability in squamous cell carcinomas of the head and neck related to field cancerization phenomena.

Microsatellite instability in squamous cell carcinomas of the head and neck related to field cancerization phenomena.
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头颈部鳞状细胞癌中的微卫星不稳定性与现场癌化现象有关。

DOI:
10.1038/bjc.1998.644
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发表时间:
1998-11
影响因子:
8.8
通讯作者:
Boiocchi, M
Boiocchi, M
中科院分区:
医学1区
文献类型:
--
作者:
Piccinin, S;Gasparotto, D;Vukosavljevic, T;Barzan, L;Sulfaro, S;Maestro, R;Boiocchi, M

文献摘要

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头颈部鳞状细胞癌(HNSCC)患者经常出现多种癌症和上呼吸道粘膜广泛的癌前病变,这种现象被称为野地癌化。在这项研究中,我们研究了遗传不稳定性在HNSCC发展中的作用,特别是在上呼吸道肿瘤多样性现象中。为此,我们分析了67例HNSCC患者5条染色体臂上20个位点定位的微卫星不稳定性(MI)和杂合性缺失(LOH),其中45例为单一癌症,22例为多发原发肿瘤。hMLH1基因可能参与遗传不稳定,并作为头颈癌中3p21缺失现象的潜在靶点。我们的数据表明,错配修复相关的遗传不稳定性在HNSCC的癌变和头颈部肿瘤的多样性中起着次要作用。此外,我们的结果排除了hMLH1基因作为MI的决定因素和作为HNSCC中3p21缺失的特定基因靶点的作用。我们的结论是,其他可能的遗传机制,如mi阴性遗传性非息肉病性结直肠癌患者的假设,可能在上呼吸道粘膜的癌变中起主要作用。
Patients affected by squamous cell carcinoma of the head and neck (HNSCC) show frequent occurrence of multiple cancers and widespread precancerous lesions in the mucosa of the upper respiratory tract, a phenomenon known as field cancerization. In this study, we investigated the role of genetic instability in the development of HNSCC and in particular in tumour multiplicity phenomena of the upper respiratory tract. For this purpose, we analysed microsatellite instability (MI) and loss of heterozygosity (LOH) at 20 loci mapping on five chromosomal arms in 67 HNSCC patients, 45 of whom had a single cancer and 22 had multiple primary tumours. The possible involvement of the hMLH1 gene in genetic instability and as a potential target of 3p21 deletion phenomena in head and neck cancers was also investigated. Our data indicate that mismatch repair-related genetic instability plays a minor role in the carcinogenesis of HNSCC and in tumour multiplicity of the head and neck region. Moreover, our results exclude a role for the hMLH1 gene as a determinant of MI and as a specific gene target of deletion at 3p21 in HNSCC. We conclude that presumably other genetic mechanisms, such as those hypothesized for MI-negative hereditary non-polyposis colorectal cancer patients, may play a major role in the carcinogenesis of the mucosa of the upper respiratory tract.