Unfavorable prognosis of CRTC1-MAML2 positive mucoepidermoid tumors with CDKN2A deletions

Genes Chromosomes Cancer. 2010 Jan;49(1):59-69. doi: 10.1002/gcc.20719.

Abstract

The CRTC1-MAML2 fusion oncogene underlies the etiology of mucoepidermoid salivary gland carcinoma (MEC) where it confers a favorable survival outcome as compared with fusion-negative MEC. While these analyses suggested that detection of CRTC1-MAML2 serves as a useful prognostic biomarker, we recently identified outlier cases of fusion-positive MEC associated with advanced-staged lethal disease. To identify additional genetic alterations that might cooperate with CRTC1-MAML2 to promote disease progression, we performed a pilot high-resolution oligonucleotide array CGH (aCGH) and PCR-based genotyping study on 23 MEC samples including 14 fusion-positive samples for which we had clinical outcome information. Unbiased aCGH analysis identified inactivating deletions within CDKN2A as a candidate poor prognostic marker which was confirmed by PCR-based analysis (CDKN2A deletions in 5/5 unfavorable fusion-positive cases and 0/9 favorable fusion-positive cases). We did not detect either activating EGFR mutations, nor copy number gains at the EGFR or ERBB2 loci as poor prognostic features for fusion-positive MEC in any of the tumor specimens. Prospective studies with larger case series will be needed to confirm that combined CRTC1-MAML2 and CDKN2A genotyping will optimally stage this disease.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Mucoepidermoid / genetics*
  • Carcinoma, Mucoepidermoid / pathology
  • Comparative Genomic Hybridization
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • ErbB Receptors
  • Female
  • Gene Deletion*
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Oncogene Proteins, Fusion*
  • Pilot Projects
  • Polymerase Chain Reaction
  • Prognosis
  • Receptor, ErbB-2
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / pathology
  • Trans-Activators
  • Transcription Factors / genetics*

Substances

  • CRTC1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA-Binding Proteins
  • MAML2 protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Trans-Activators
  • Transcription Factors
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2