title: Unfavorable prognosis of CRTC1-MAML2 positive mucoepidermoid tumors with CDKN2A deletions.
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.
authors.affiliation: Genetics Branch, Center for Cancer Research, NCI, Bethesda, MD.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Anzick
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Chen
authors.forename: Yoonsoo
authors.initials: Y
authors.lastname: Park
authors.forename: Paul
authors.initials: P
authors.lastname: Meltzer
authors.forename: Diana
authors.initials: D
authors.lastname: Bell
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Kaye
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D066246:ErbB Receptors; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D014157:Transcription Factors; C500984:CRTC1 protein, human; C471297:MAML2 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human