Gray Sarah E, Kay Elaine, Leader Mary, Mabruk Mohamed
Molecular Oncology Laboratory, Pathology Department, Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin, Ireland.
J Cutan Pathol. 2008 Jan;35(1):1-9. doi: 10.1111/j.1600-0560.2007.00760.x.
Germ line mutations of the BRCA2 tumor suppressor gene with subsequent loss of the remaining wild-type BRCA2 allele have been identified in up to 35% of familial breast cancer cases. A high frequency of allelic loss at the BRCA2 gene locus has also been reported in a variety of sporadic epithelial tumors including oesophageal squamous cell carcinomas (SCC), and sporadic head and neck SCC.
The present study aimed to examine the integrity of the BRCA2 gene in cutaneous SCC.
Allelic imbalance/loss of heterozygosity (AI/LOH) was examined in 22 histologically confirmed cutaneous SCC at two microsatellite markers, D13S260 (centromeric to the BRCA2 gene) and D13S267 (telomeric to the BRCA2 gene). Immunohistochemical analysis of BRCA2 protein expression was also examined in the cutaneous SCC.
AI/LOH at the D13S260 locus was found in eight of the 19 informative SCC, and AI/LOH at the D13S267 locus was found in 12 of the 18 informative SCC. Seven SCC showed allelic loss at both markers, and six SCC showed retention of heterozygosity at both markers. Expression of BRCA2 protein was only detected in six of the normal epidermises and three of the 21 SCC examined.
AI/LOH of the BRCA2 gene region was found to be common in the cutaneous SCC.
在高达35%的家族性乳腺癌病例中已发现BRCA2肿瘤抑制基因的种系突变，随后剩余的野生型BRCA2等位基因丢失。在包括食管鳞状细胞癌（SCC）和散发性头颈部SCC在内的多种散发性上皮肿瘤中，也报道了BRCA2基因位点的高频等位基因缺失。
本研究旨在检测皮肤SCC中BRCA2基因的完整性。
在22例经组织学确诊的皮肤SCC中，检测两个微卫星标记D13S260（BRCA2基因着丝粒侧）和D13S267（BRCA2基因端粒侧）的等位基因不平衡/杂合性缺失（AI/LOH）。还对皮肤SCC进行了BRCA2蛋白表达的免疫组织化学分析。
在19例信息性SCC中的8例中发现D13S260位点存在AI/LOH，在18例信息性SCC中的12例中发现D13S267位点存在AI/LOH。7例SCC在两个标记处均显示等位基因缺失，6例SCC在两个标记处均显示杂合性保留。仅在6例正常表皮和21例检测的SCC中的3例中检测到BRCA2蛋白表达。
发现BRCA2基因区域的AI/LOH在皮肤SCC中很常见。
