title: Novel chromosomal rearrangements and break points at the t(6;9) in salivary adenoid cystic carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome.
abstract: OBJECTIVE
  To investigate the molecular genetic heterogeneity associated with the t(6:9) in adenoid cystic carcinoma (ACC) and correlate the findings with patient clinical outcome.
  
  
  METHODS
  Multimolecular and genetic techniques complemented with massive pair-ended sequencing and single-nucleotide polymorphism array analyses were used on tumor specimens from 30 new and 52 previously analyzed fusion transcript-negative ACCs by reverse transcriptase PCR (RT-PCR). MYB mRNA expression level was determined by quantitative RT-PCR. The results of 102 tumors (30 new and 72 previously reported cases) were correlated with the clinicopathologic factors and patients' survival.
  
  
  RESULTS
  The FISH analysis showed 34 of 82 (41.5%) fusion-positive tumors and molecular techniques identified fusion transcripts in 21 of the 82 (25.6%) tumors. Detailed FISH analysis of 11 out the 15 tumors with gene fusion without transcript formation showed translocation of NFIB sequences to proximal or distal sites of the MYB gene. Massive pair-end sequencing of a subset of tumors confirmed the proximal translocation to an NFIB sequence and led to the identification of a new fusion gene (NFIB-AIG1) in one of the tumors. Overall, MYB-NFIB gene fusion rate by FISH was in 52.9% whereas fusion transcript forming incidence was 38.2%. Significant statistical association between the 5' MYB transcript expression and patient survival was found.
  
  
  CONCLUSIONS
  We conclude that: (i) t(6;9) results in complex genetic and molecular alterations in ACC, (ii) MYB-NFIB gene fusion may not always be associated with chimeric transcript formation, (iii) noncanonical MYB-NFIB gene fusions occur in a subset of tumors, (iv) high MYB expression correlates with worse patient survival.
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Yoshitsugu
authors: Y
authors: Mitani
authors: Pulivarthi H
authors: PH
authors: Rao
authors: P Andrew
authors: PA
authors: Futreal
authors: Dianna B
authors: DB
authors: Roberts
authors: Philip J
authors: PJ
authors: Stephens
authors: Yi-Jue
authors: YJ
authors: Zhao
authors: Li
authors: L
authors: Zhang
authors: Mutsumi
authors: M
authors: Mitani
authors: Randal S
authors: RS
authors: Weber
authors: Scott M
authors: SM
authors: Lippman
authors: Carlos
authors: C
authors: Caulin
authors: Adel K
authors: AK
authors: El-Naggar
mesh_terms: D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000401:mortality; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D050939:Gene Fusion; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000401:mortality; D014178:Translocation, Genetic
chemical_list: C545202:MYB-NFIB fusion protein, human; D015514:Oncogene Proteins, Fusion