Danaee Hadi, Karagas Margaret R, Kelsey Karl T, Perry Ann E, Nelson Heather H
Department of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
J Invest Dermatol. 2006 May;126(5):1152-8. doi: 10.1038/sj.jid.5700209.
The human homolog of the Drosophila Patched gene (PTCH), located at chromosome 9q22.3, is frequently altered in both nevoid basal cell carcinoma syndrome, and sporadic basal cell carcinomas (BCCs). However, alteration of the PTCH gene locus has been poorly studied in squamous cell carcinoma (SCC). We analyzed loss of heterozygosity (LOH) at five markers in and around the PTCH gene in 276 keratinocyte tumors from a population-based study in New Hampshire. We found a high prevalence of any 9q22.3 LOH in both BCC (75.5%) and SCC (60.8%), with BCC being significantly more likely to have LOH than SCC (P<0.009). The PTCH gene was specifically lost in 60% of BCC, and 50% of SCC tumors. Among SCC tumors, 9q22 LOH was significantly more likely to occur in those who tend to burn (P<0.05), and this association was strongest for tumors that occurred on sun-exposed areas of the body (P<0.04). Additionally, 9q22 LOH occurred more frequently in SCC tumors associated with a history of severe sunburns (P<0.08). Thus, in our large, population-based sample, 9q22 loss, including PTCH, was highly prevalent in both BCC and SCC. Overall, these data support the hypothesis that PTCH loss is a common, early lesion for SCC and BCC.
果蝇patched基因（PTCH）的人类同源基因位于9号染色体q22.3，在痣样基底细胞癌综合征和散发性基底细胞癌（BCC）中经常发生改变。然而，PTCH基因位点的改变在鳞状细胞癌（SCC）中的研究较少。我们在新罕布什尔州一项基于人群的研究中，分析了276例角质形成细胞肿瘤中PTCH基因及其周围五个标记的杂合性缺失（LOH）情况。我们发现BCC（75.5%）和SCC（60.8%）中9q22.3 LOH的发生率都很高，BCC发生LOH的可能性显著高于SCC（P<0.009）。PTCH基因在60%的BCC和50%的SCC肿瘤中特异性缺失。在SCC肿瘤中，9q22 LOH在容易晒伤的患者中更易发生（P<0.05），这种关联在身体暴露于阳光部位发生的肿瘤中最为显著（P<0.04）。此外，9q22 LOH在有严重晒伤史的SCC肿瘤中更频繁发生（P<0.08）。因此，在我们基于人群的大样本中，包括PTCH在内的9q22缺失在BCC和SCC中都非常普遍。总体而言，这些数据支持PTCH缺失是SCC和BCC常见的早期病变这一假说。
