Mayo Clinic College of Medicine, Scottsdale, Arizona, USA.
Cancer Prev Res (Phila). 2010 Oct;3(10):1277-83. doi: 10.1158/1940-6207.CAPR-10-0058. Epub 2010 Sep 28.
Cutaneous squamous cell carcinoma (SCC) occurs commonly and can metastasize. Identification of specific molecular aberrations and mechanisms underlying the development and progression of cutaneous SCC may lead to better prognostic and therapeutic approaches and more effective chemoprevention strategies. To identify genetic changes associated with early stages of cutaneous SCC development, we analyzed a series of 40 archived skin tissues ranging from normal skin to invasive SCC. Using high-resolution array-based comparative genomic hybridization, we identified deletions of a region on chromosome 10q harboring the INPP5A gene in 24% of examined SCC tumors. Subsequent validation by immunohistochemistry on an independent sample set of 71 SCC tissues showed reduced INPP5A protein levels in 72% of primary SCC tumors. Decrease in INPP5A protein levels seems to be an early event in SCC development, as it also is observed in 9 of 26 (35%) examined actinic keratoses, the earliest stage in SCC development. Importantly, further reduction of INPP5A levels is seen in a subset of SCC patients as the tumor progresses from primary to metastatic stage. The observed frequency and pattern of loss indicate that INPP5A, a negative regulator of inositol signaling, may play a role in development and progression of cutaneous SCC tumors.
皮肤鳞状细胞癌（SCC）较为常见，且可能发生转移。鉴定皮肤 SCC 发生和发展过程中特定的分子异常和机制，可能会为预后和治疗方法提供更好的选择，并制定出更有效的化学预防策略。为了鉴定与皮肤 SCC 早期发展相关的遗传变化，我们分析了 40 个存档的皮肤组织，范围从正常皮肤到侵袭性 SCC。通过使用高分辨率基于阵列的比较基因组杂交技术，我们鉴定出在 24%的检查 SCC 肿瘤中，10q 染色体上包含 INPP5A 基因的区域存在缺失。随后，在 71 例 SCC 组织的独立样本集上通过免疫组织化学进行验证，显示在 72%的原发性 SCC 肿瘤中 INPP5A 蛋白水平降低。INPP5A 蛋白水平的降低似乎是 SCC 发展的早期事件，因为在 SCC 发展的最早阶段，即 26 例光化性角化病中的 9 例中也观察到了这种情况。重要的是，在一部分 SCC 患者中，随着肿瘤从原发性进展到转移性阶段，INPP5A 水平进一步降低。观察到的缺失频率和模式表明，INPP5A 是一种肌醇信号的负调节剂，可能在皮肤 SCC 肿瘤的发生和发展中发挥作用。
