Molecular signatures linked with aggressive behavior in basal cell carcinoma: A report of 6 cases

Helen Fernandes, Neil Fernandes, Siddharth Bhattacharya, Wen Chen, Anjali Seth, Meera Hameed, Neena Mirani, W. Clark Lambert

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

A small subset of basal cell carcinoma (BCC) characterized by rapid growth, recurrence, deep local invasiveness to dura, and/or bone is classified as extremely aggressive. Histologically, exclusive of invasive sites these tumors are similar to nonaggressive BCC. In the present study, we compare the molecular signatures of these 2 types of tumors. Twenty-one BCC specimens, 6 aggressive and 15 nonaggressive, were used in the study. DNA was extracted from formalin-fixed paraffin-embedded sections of 21 pairs of normal and tumor tissue. The specimens were subjected to loss of heterozygosity (LOH) analysis on chromosome 9q22 in the PATCHED gene. Regulatory single nucleotide polymorphisms (SNPs) at -308 in the tumor necrosis factor alpha and -1082 in the interleukin 10 genes were examined. LOH at one or more markers was observed in all 6 of the aggressive specimens compared with 2 of the 15 nonaggressive BCC specimens. A total of 63.6% of all heterozygous markers in the aggressive tumors showed LOH compared with 17.9% of the nonaggressive BCC. The tumor necrosis factor alpha -238 SNP and the interleukin 10 -1082 SNP were more prevalent in aggressive BCC. The results of this pilot study indicate that LOH at chromosome 9q22 is a potential marker for the identification of aggressive behavior in BCCs. Furthermore, our study suggests that cytokine SNPs may be used to stratify risk in the assessment of aggressiveness in BCC.

Original languageEnglish
Pages (from-to)550-556
Number of pages7
JournalAmerican Journal of Dermatopathology
Volume32
Issue number6
DOIs
StatePublished - Aug 2010
Externally publishedYes

Keywords

  • aggressive
  • allelic loss
  • basal cell carcinoma
  • cytokines
  • proinflammatory

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