1. ¹Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, USA
2. ²Department of Community and Family Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA
3. ³Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire, USA
4. ⁴Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA

Correspondence: Dr Heather H. Nelson, Harvard School of Public Health, 665 Huntington Avenue, Bldg. 1, Rm. 603, Boston, Massachusetts 02115-6021, USA. E-mail: hnelson@hsph.harvard.edu

Received 30 June 2005; Revised 7 December 2005; Accepted 12 December 2005; Published online 16 February 2006.

Abstract

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.