Genomic analysis of atypical fibroxanthoma

PLoS One. 2017 Nov 15;12(11):e0188272. doi: 10.1371/journal.pone.0188272. eCollection 2017.

Abstract

Atypical fibroxanthoma (AFX), is a rare type of skin cancer affecting older individuals with sun damaged skin. Since there is limited genomic information about AFX, our study seeks to improve the understanding of AFX through whole-exome and RNA sequencing of 8 matched tumor-normal samples. AFX is a highly mutated malignancy with recurrent mutations in a number of genes, including COL11A1, ERBB4, CSMD3, and FAT1. The majority of mutations identified were UV signature (C>T in dipyrimidines). We observed deletion of chromosomal segments on chr9p and chr13q, including tumor suppressor genes such as KANK1 and CDKN2A, but no gene fusions were found. Gene expression profiling revealed several biological pathways that are upregulated in AFX, including tumor associated macrophage response, GPCR signaling, and epithelial to mesenchymal transition (EMT). To further investigate the presence of EMT in AFX, we conducted a gene expression meta-analysis that incorporated RNA-seq data from dermal fibroblasts and keratinocytes. Ours is the first study to employ high throughput sequencing for molecular profiling of AFX. These data provide valuable insights to inform models of carcinogenesis and additional research towards tumor-directed therapy.

MeSH terms

  • 3' Untranslated Regions
  • Cadherins / genetics
  • Collagen Type XI / genetics
  • Epithelial-Mesenchymal Transition
  • Exome Sequencing
  • Genome, Human*
  • Humans
  • Membrane Proteins / genetics
  • Mutation
  • Receptor, ErbB-4 / genetics
  • Sequence Analysis, RNA
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Transcriptome

Substances

  • 3' Untranslated Regions
  • COL11A1 protein, human
  • CSMD3 protein, human
  • Cadherins
  • Collagen Type XI
  • FAT1 protein, human
  • Membrane Proteins
  • ERBB4 protein, human
  • Receptor, ErbB-4