PMID- 18059337
OWN - NLM
STAT- MEDLINE
DCOM- 20080806
LR  - 20100526
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 27
IP  - 21
DP  - 2008 May 8
TI  - High-resolution array CGH analysis of salivary gland tumors reveals fusion and 
      amplification of the FGFR1 and PLAG1 genes in ring chromosomes.
PG  - 3072-80
AB  - 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.
FAU - Persson, F
AU  - Persson F
AD  - Lundberg Laboratory for Cancer Research, Department of Pathology, Sahlgrenska 
      University Hospital, Goteborg University, Goteborg, Sweden.
FAU - Winnes, M
AU  - Winnes M
FAU - Andren, Y
AU  - Andren Y
FAU - Wedell, B
AU  - Wedell B
FAU - Dahlenfors, R
AU  - Dahlenfors R
FAU - Asp, J
AU  - Asp J
FAU - Mark, J
AU  - Mark J
FAU - Enlund, F
AU  - Enlund F
FAU - Stenman, G
AU  - Stenman G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071203
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (PLAG1 protein, human)
RN  - EC 2.7.10.1 (FGFR1 protein, human)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1)
SB  - IM
MH  - DNA-Binding Proteins/*genetics
MH  - *Gene Fusion
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Nucleic Acid Hybridization
MH  - Receptor, Fibroblast Growth Factor, Type 1/*genetics
MH  - *Ring Chromosomes
MH  - Salivary Gland Neoplasms/*genetics/pathology
EDAT- 2007/12/07 09:00
MHDA- 2008/08/07 09:00
CRDT- 2007/12/07 09:00
PHST- 2007/12/07 09:00 [pubmed]
PHST- 2008/08/07 09:00 [medline]
PHST- 2007/12/07 09:00 [entrez]
AID - 1210961 [pii]
AID - 10.1038/sj.onc.1210961 [doi]
PST - ppublish
SO  - Oncogene. 2008 May 8;27(21):3072-80. doi: 10.1038/sj.onc.1210961. Epub 2007 Dec 
      3.