Takata M, Rehman I, Rees J L
Department of Dermatology, Kanazawa University School of Medicine, Japan.
Hum Pathol. 1998 Feb;29(2):193-5. doi: 10.1016/s0046-8177(98)90234-9.
The genetic events responsible for tumor progression may be defined by careful analysis of genetic changes in well-chosen tumors which contain distinct cell populations representing each stage of progression. Here we report a case of a trichilemmal carcinoma arising in the wall of a proliferating trichilemmal cyst (PTC). DNA was isolated from microdissected areas of the PTC and the carcinoma respectively, and PCR-based microsatellite loss of heterozygosity (LOH) analysis as well as p53 gene sequencing performed. A CGA to TGA nonsense mutation at codon 306 in exon 8 of the p53 gene was found in both samples. LOH analysis showed that the PTC retained chromosome arm 17p (where the p53 gene resides), whereas the carcinoma was associated with the loss of this allele. All the other loci examined were retained including 3p, 9q, 13q and 17q in both tumor parts. The results confirm a common clonal origin of the PTC and the trichilemmal carcinoma, and strongly suggest that the complete loss of the wild-type p53 is a critical event responsible for malignant transformation in this particular case.
通过对精心挑选的肿瘤进行基因变化的仔细分析，可以确定导致肿瘤进展的基因事件，这些肿瘤包含代表进展各阶段的不同细胞群体。在此，我们报告一例发生于增生性毛鞘囊肿（PTC）壁的毛鞘癌病例。分别从PTC和癌的显微切割区域分离DNA，并进行基于聚合酶链反应（PCR）的微卫星杂合性缺失（LOH）分析以及p53基因测序。在两个样本中均发现p53基因第8外显子306密码子处存在从CGA到TGA的无义突变。LOH分析显示，PTC保留了17号染色体短臂（p53基因所在位置），而癌则与该等位基因的缺失相关。在两个肿瘤部分中，所有其他检测位点均保留，包括3号染色体短臂、9号染色体长臂、13号染色体长臂和17号染色体长臂。结果证实了PTC和毛鞘癌有共同的克隆起源，并强烈表明在该特定病例中野生型p53的完全缺失是导致恶性转化的关键事件。
