Ahmadian A, Ren Z P, Williams C, Pontén F, Odeberg J, Pontén J, Uhlén M, Lundeberg J
Department of Biochemistry and Biotechnology, Royal Institute of Technology, Stockholm, Sweden.
Oncogene. 1998 Oct 8;17(14):1837-43. doi: 10.1038/sj.onc.1202080.
Squamous cell carcinoma (SCC) of the skin represents a group of neoplasms which is associated with exposure to UV light. Recently, we obtained data suggesting that invasive skin cancer and its precursors derive from one original neoplastic clone. Here, the analysis were extended by loss of heterozygosity (LOH) analysis in the chromosome 9q22.3 region. A total of 85 samples, taken from twenty-two sections of sun-exposed sites, corresponding to normal epidermis, morphological normal cells with positive immuno-staining for the p53 protein (p53 patches), dysplasias, cancer in situ (CIS) and squamous cell carcinomas (SCC) of the skin were analysed. Overall, about 70% of p53 patches had mutations in the p53 gene but not LOH in the p53 gene or 9q22.3 region. Approximately 70% of the dysplasias showed p53 mutations of which about 40% had LOH in the p53 region but not in the 9q22.3 region. In contrast, about 65% of SCC and CIS displayed LOH in the 9q22.3 region, as well as frequent (80%) mutations and/or LOH in the p53 gene. These findings strongly suggest that alterations in the p53 gene is an early event in the progression towards SCC, whereas malignant development involves LOH and alterations in at least one (or several) tumor suppressor genes located in chromosome 9q22.3.
皮肤鳞状细胞癌（SCC）是一组与紫外线暴露相关的肿瘤。最近，我们获得的数据表明侵袭性皮肤癌及其前体源自一个原始的肿瘤克隆。在此，通过对9q22.3染色体区域的杂合性缺失（LOH）分析扩展了研究。共分析了85个样本，取自22个暴露于阳光部位的切片，分别对应正常表皮、p53蛋白免疫染色阳性的形态学正常细胞（p53斑块）、发育异常、原位癌（CIS）和皮肤鳞状细胞癌（SCC）。总体而言，约70%的p53斑块存在p53基因突变，但p53基因或9q22.3区域无杂合性缺失。约70%的发育异常显示p53突变，其中约40%在p53区域存在杂合性缺失，但在9q22.3区域无缺失。相反，约65%的SCC和CIS在9q22.3区域显示杂合性缺失，以及p53基因频繁（80%）发生突变和/或杂合性缺失。这些发现强烈表明，p53基因改变是向SCC进展过程中的早期事件，而恶性发展涉及9q22.3染色体上至少一个（或几个）肿瘤抑制基因的杂合性缺失和改变。
