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Göteborgs universitets publikationer

Clinically significant copy number alterations and complex rearrangements of MYB and NFIB in head and neck adenoid cystic carcinoma.

Författare och institution:
Marta Persson (Institutionen för biomedicin, avdelningen för patologi & Sahlgrenska Cancer Center); Ywonne Andrén (Institutionen för biomedicin, avdelningen för patologi & Sahlgrenska Cancer Center); Christopher A Moskaluk (-); Henry F Frierson (-); Susanna L Cooke (-); Philip Andrew Futreal (-); Teresia Kling (Institutionen för medicin, avdelningen för molekylär och klinisk medicin & Sahlgrenska Cancer Center); Sven Nelander (Institutionen för medicin, avdelningen för molekylär och klinisk medicin & Sahlgrenska Cancer Center); Anders Nordkvist (Institutionen för biomedicin, avdelningen för patologi & Sahlgrenska Cancer Center); Fredrik Persson (Sahlgrenska Cancer Center); Göran Stenman (Sahlgrenska Cancer Center)
Publicerad i:
Genes, chromosomes & cancer, 51 ( 8 ) s. 805-17
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Adenoid cystic carcinoma (ACC) of the head and neck is a malignant tumor with poor long-term prognosis. Besides the recently identified MYB-NFIB fusion oncogene generated by a t(6;9) translocation, little is known about other genetic alterations in ACC. Using high-resolution, array-based comparative genomic hybridization, and massively paired-end sequencing, we explored genomic alterations in 40 frozen ACCs. Eighty-six percent of the tumors expressed MYB-NFIB fusion transcripts and 97% overexpressed MYB mRNA, indicating that MYB activation is a hallmark of ACC. Thirty-five recurrent copy number alterations (CNAs) were detected, including losses involving 12q, 6q, 9p, 11q, 14q, 1p, and 5q and gains involving 1q, 9p, and 22q. Grade III tumors had on average a significantly higher number of CNAs/tumor compared to Grade I and II tumors (P = 0.007). Losses of 1p, 6q, and 15q were associated with high-grade tumors, whereas losses of 14q were exclusively seen in Grade I tumors. The t(6;9) rearrangements were associated with a complex pattern of breakpoints, deletions, insertions, inversions, and for 9p also gains. Analyses of fusion-negative ACCs using high-resolution arrays and massively paired-end sequencing revealed that MYB may also be deregulated by other mechanisms in addition to gene fusion. Our studies also identified several down-regulated candidate tumor suppressor genes (CTNNBIP1, CASP9, PRDM2, and SFN) in 1p36.33-p35.3 that may be of clinical significance in high-grade tumors. Further, studies of these and other potential target genes may lead to the identification of novel driver genes in ACC.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper
Adult, Aged, Aged, 80 and over, Carcinoma, Adenoid Cystic, genetics, Comparative Genomic Hybridization, DNA Copy Number Variations, Female, Gene Rearrangement, Genes, Tumor Suppressor, Genes, myb, Head and Neck Neoplasms, genetics, Humans, Male, Middle Aged, NFI Transcription Factors, genetics, Oncogene Proteins, Fusion, genetics, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction
Postens nummer:
Posten skapad:
2013-01-04 15:27
Posten ändrad:
2013-01-18 11:06

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