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Rehan Hussain, Jared Matthews, Sander Dubovy, Gaofeng Wang; UV-Independent p53 Mutations in Sebaceous Carcinoma of the Eyelid. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6212.
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Sebaceous carcinoma (SC) is a potentially fatal neoplasm that has a tendency to arise in the eyelid. UV exposure and mutations of the p53 gene have been implicated in SC . Kiyosaki et al reported a high frequency (67%) of p53 mutations in SC from Asian patients . Most identified mutations of p53 in SC are point mutations, which are distinct from tandem mutations caused by UV exposure [1-3]. We analyzed p53 mutations in 14 cases to study the relationship between the frequency of p53 mutations and SC of the eyelid of Caucasians.
Sebaceous carcinoma of the eyelid resected from 14 Caucasian patients at Bascom Palmer Eye Institute from 1994 - 2010 were reviewed. An ophthalmic pathologist (SRD) performed histologic evaluation of each specimen. Carcinoma tissues were cut out by sterilized needles. Genomic DNA was extracted from paraffin-embedded tissues. PCR primers were chosen from a published study . All 11 exons including flanking intronic regions were amplified by PCR and sequenced in both directions. Sequencing traces were analyzed. Sequence aberrations were confirmed by re-PCR and re-sequencing.
Of the 14 SC samples, 7 were found to have p53 mutations (Table 1). Four specimens were found to have one p53 mutation. Two samples carried two mutations. One sample was identified with three missense mutations. We examined whether there is a possible relationship between the severity of p53 mutations and pathological features. We did not find any correlation between p53 mutations and pathologic features, tumor size, stage, recurrence or metastasis.
A high frequency of p53 mutations have been reported in SC of the eyelid from Asian patients . Our data suggest that the frequency of p53 mutation is also high (50%) in SC from Caucasian patients. Mutations of p53 identified in previous studies are point mutations. In addition to 7 novel point mutations, a 9 bp deletion and a 6 bp insertion are also identified in our samples. No mutations are tandem mutations, suggesting that aberrant p53 is likely UV independent. There is no obvious correlation between severity of p53 mutations and pathological characterizations. The results suggest that UV independent mutations in p53 could be a pathogenic factor for SC of the eyelid.
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