Details

Autor(en) / Beteiligte

• Persson, F
• Winnes, M
• Andrén, Y
• Wedell, B
• Dahlenfors, R
• Asp, J
• Mark, J
• Enlund, F
• Stenman, G

Titel

High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes

Ist Teil von

• Oncogene, 2008-05, Vol.27 (21), p.3072-3080

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• We have previously identified a subgroup of pleomorphic salivary gland adenomas with ring chromosomes of uncertain derivation. Here, we have used spectral karyotyping (SKY), fluorescence in situ hybridization (FISH) and high-resolution oligonucleotide array-CGH to determine the origin and content of these rings and to identify genes disrupted as a result of ring formation. Of 16 tumors with rings, 11 were derived from chromosome 8, 3 from chromosome 5 and 1 each from chromosomes 1, 6 and 9. Array-CGH revealed that 10/11 r(8) consisted of amplification of a 19 Mb pericentromeric segment with recurrent breakpoints in FGFR1 in 8p12 and in PLAG1 in 8q12.1. Molecular analyses revealed that ring formation consistently generated novel FGFR1–PLAG1 gene fusions in which the 5′-part of FGFR1 is linked to the coding sequence of PLAG1 . An alternative mechanism of PLAG1 activation was found in tumors with copy number gain of an intact PLAG1 gene. Rings derived from chromosomes 1, 5, 6 or 9 did not result in gene fusions, but rather resulted in losses indicative of the involvement of putative tumor suppressor genes on 8p, 5p, 5q and/or 6q. Our findings also reveal a novel mechanism by which FGFR1 contributes to oncogenesis and further illustrate the versatility of the FGFR1 and PLAG1 genes in tumorigenesis.