Holmberg E, Rozell B L, Toftgård R
Department of Bioscience, Karolinska Institute, Huddinge, Sweden.
Br J Cancer. 1996 Jul;74(2):246-50. doi: 10.1038/bjc.1996.345.
Familial predisposition to basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin are apparent in the autosomal dominant syndromes naevoid basal cell carcinoma syndrome (NBCCS) and multiple self-healing squamous epitheliomata (MSSE) respectively. The gene responsible for NBCCS has been proposed to be a tumour-suppressor gene and is mapped to the same 2 Mb interval on 9q22.3 as the MSSE gene ESS1. In an attempt to further map the NBCCS gene, we have examined loss of heterozygosity (LOH) in 16 sporadic BCCs and two familial BCCs using microsatellite markers located within the candidate gene region. The overall frequency of LOH observed was 67% in the BCCs and partial or interstitial deletions were found in eight tumours, with the highest LOH frequency at markers D9S280, D9S287 and D9S180. To determine if the same genomic region also shows frequent LOH in tumours with a squamous phenotype, we have examined 11 SCCs, four actinic keratoses and 13 cases of Bowen's disease for LOH at 9q22.3. An overall LOH frequency of 50% was observed at D9S180, and occurred in all types of squamous tumours. In contrast, a much lower LOH frequency of only 6% was found at the D9S287 locus. Our observation of different patterns of LOH at 9q22.3 in sporadic BCCs and SCCs implies that more than one tumour-suppressor gene might be located in this genomic region.
皮肤基底细胞癌（BCC）和鳞状细胞癌（SCC）的家族易感性分别在常染色体显性综合征痣样基底细胞癌综合征（NBCCS）和多发性自愈性鳞状上皮瘤（MSSE）中表现明显。负责NBCCS的基因被认为是一种肿瘤抑制基因，并且与MSSE基因ESS1一样被定位到9q22.3上相同的2 Mb区间。为了进一步定位NBCCS基因，我们使用位于候选基因区域内的微卫星标记，检测了16例散发性BCC和2例家族性BCC中的杂合性缺失（LOH）。在BCC中观察到的LOH总体频率为67%，在8个肿瘤中发现了部分或间质性缺失，在标记D9S280、D9S287和D9S180处LOH频率最高。为了确定相同的基因组区域在具有鳞状表型的肿瘤中是否也显示出频繁的LOH，我们检测了11例SCC、4例光化性角化病和13例鲍恩病在9q22.3处的LOH。在D9S180处观察到的总体LOH频率为50%，并且在所有类型的鳞状肿瘤中都出现。相比之下，在D9S287位点发现的LOH频率要低得多，仅为6%。我们在散发性BCC和SCC中观察到9q22.3处不同的LOH模式，这意味着该基因组区域可能存在不止一个肿瘤抑制基因。
