Höglund Mattias, Jin Charlotte, Gisselsson David, Hansen Gunnar B, Mitelman Felix, Mertens Fredrik
Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden.
Cancer Genet Cytogenet. 2004 Apr 1;150(1):1-8. doi: 10.1016/j.cancergencyto.2003.08.012.
More than 250 head and neck squamous cell carcinomas (HNSCCs) with clonal chromosomal abnormalities have been reported. Even though the pattern of aberrations is nonrandom, no specific primary or secondary karyotypic abnormalities have been identified. One explanation for the still-rudimentary understanding of the cytogenetic evolution in HNSCC could be the pronounced karyotypic complexity seen in these tumors. In an attempt to overcome this difficulty, we have applied several statistical methods such as hierarchical cluster analysis, multidimensional scaling, and k-means clustering, which allow the identification and interpretation of karyotypic pathways, as well as establishing a temporal order of chromosomal imbalances on 241 published and 70 previously unpublished HNSCC karyotypes. From the analysis of the distribution of the number of imbalances per tumor we suggest that the carcinomas evolve through three phases representing different stages of chromosomal instability. Two major cytogenetic pathways, one dominated by gains and another by losses, were identified by means of principal component analysis. These were initiated by +7 and by any of the aberrations 1p-, 3p-, or 7q-, respectively.
据报道，超过250例头颈部鳞状细胞癌（HNSCC）存在克隆性染色体异常。尽管畸变模式并非随机，但尚未发现特定的原发性或继发性核型异常。对HNSCC细胞遗传学进化仍了解不足的一个原因可能是这些肿瘤中明显的核型复杂性。为了克服这一困难，我们应用了几种统计方法，如层次聚类分析、多维标度法和k均值聚类法，这些方法能够识别和解释核型途径，并确定241个已发表和70个先前未发表的HNSCC核型中染色体不平衡的时间顺序。通过分析每个肿瘤中不平衡数量的分布，我们认为这些癌通过代表染色体不稳定不同阶段的三个阶段进化。通过主成分分析确定了两条主要的细胞遗传学途径，一条以增加为主，另一条以缺失为主。它们分别由+7以及1p-、3p-或7q-中的任何一种畸变引发。
