Allelic Loss at Drosophila Patched Gene Is Highly Prevalent in Basal and Squamous Cell Carcinomas of the Skin

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.

Skin Cancer: New Markers for Better Prevention

“…0.08). Overall, these data support the hypothesis that loss of PTCH is a common, early lesion for SCC and BCC [82] , and that chromosomal alterations in certain gene loci might be used as biomarker for UV (sun) exposure in the past [for example, if they appear in persisting epidermal (stem) cells].…”

“…The human homolog of the Dro-sophila patched gene (PTCH) , located at chromosome 9q22.3, is frequently altered in both nevoid BCC syndrome and sporadic BCCs. Danaee et al [82] also studied alterations of the PTCH gene locus in SCC. They analyzed LOH at 5 markers in and around the PTCH gene in 276 keratinocyte tumors and found a high prevalence of a LOH at 9q22.3 in both BCC (75.5%) and SCC (60.8%).…”

The anaplastic lymphoma kinase as an oncogene in solid tumors

“…The prevalence of LOH was 50% for BCC, and 27.27% for OC. In literature the prevalence of LOH in BCCs is between 35 and 75% (40,22,41,42,26) and 70% for ovarian tumors, both benign and malignant (30). Our data is comparable with published data for BCC, but is significantly lower for OC.…”

“…Sporadic mutations of the PTCH1 gene are involved in a series of sporadic tumors, including BCC (21,22), medulloblastomas (23), skin trichoepitheliomas (24), esophageal squamous cell carcinomas (25), squamous cell carcinomas (26), breast cancer (23), as well as in odontogenic keratocysts (27).…”

Mechanisms of Inactivation of PTCH1 Gene in Nevoid Basal Cell Carcinoma Syndrome: Modification of the Two-Hit Hypothesis

“…Our previous studies (9)(10)(11)(12), as well as others (13)(14)(15), have revealed that >85% of NBCCS-associated KCOTs and nearly 30% of sporadic KCOTs harbored PTCH1 mutations. In addition, loss of heterozygosity (LOH) at chromosome 9q22-31, the region to which the PTCH1 gene maps, has been observed as a frequent event in NBCCS-associated tumors, although different estimates of the prevalence of LOH (16-75%) were reported (8,(16)(17)(18). Besides, research on NBCCS-related primitive neuroectodermal tumors has shown that PTCH1 mutations occurred predominantly in tumors with LOH at 9q22 (17).…”