Sasiadek Maria M, Smigiel Robert, Stembalska Agnieszka, Ramsey David, Blin Nikolaus
Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1, 50-368, Wroclaw, Poland.
Anticancer Res. 2006 Nov-Dec;26(6B):4597-601.
Carcinogenesis results from the accumulation of genetic alterations forming a functional network leading to genetic instability as a cardinal feature. Thus, the hypothesis that down-regulation of MLH1 in combination with aberrant cell cycle control may contribute to chromosomal instability in LSCC was tested.
Fifty-two patients, diagnosed with primary LSCC, none of whom had a history of hereditary cancer, were evaluated by comparative genomics. The expression of selected proteins controlling the cell cycle and mismatch repair was assessed with immunostaining.
In our set, 1720 chromosomal imbalances were found, as well as altered protein synthesis including a decrease in RB1 and CDKN2A (10.2% and 44% of cases, respectively), an increase in CCND1 (47%) and a decrease in MLH1 (22.7%). Variation analysis correlating proteins, chromosomal imbalances and clinicohistopathological features of disease disclosed an association between chromosomal gains, low histopathological grade of tumour and CCND1 over-expression accompanied by a decrease in MLH1 expression (p < 0.01).
CCND1 and MLH1 seem functionally interconnected in regard to chromosomal imbalances in larynx cancer.
癌症发生是由于基因改变的积累形成一个功能网络，导致基因不稳定成为主要特征。因此，我们检验了一种假说，即MLH1下调与异常的细胞周期调控相结合可能导致喉鳞状细胞癌（LSCC）的染色体不稳定。
52例被诊断为原发性LSCC且无遗传性癌症病史的患者接受了比较基因组学评估。通过免疫染色评估了控制细胞周期和错配修复的特定蛋白质的表达。
在我们的研究组中，发现了1720处染色体失衡，以及蛋白质合成改变，包括RB1和CDKN2A减少（分别占病例的10.2%和44%）、CCND1增加（47%）和MLH1减少（22.7%）。对蛋白质、染色体失衡和疾病临床组织病理学特征进行的变异分析揭示，染色体增加、肿瘤组织病理学低分级与CCND1过表达且伴有MLH1表达减少之间存在关联（p < 0.01）。
在喉癌的染色体失衡方面，CCND1和MLH1似乎在功能上相互关联。
