Expression of PLAG1 and HMGIC proteins and fusion transcripts in radiation-associated pleomorphic adenomas.
Extensive cytogenetic investigations of pleomorphic adenomas of the salivary glands have unequivocally demonstrated that they are cytogenetically monoclonal and are characterized by a high frequency of tumor specific chromosome abnormalities involving in particular chromosome bands 3p21, 8q12 and 12q14-15. Here we show that two radiation-associated and cytogenetically polyclonal adenomas without gross rearrangements of these breakpoints show simultaneous overexpression of the PLAG1 and HMGIC genes, i.e. the target genes of the 8q12 and 12q14-15 rearrangements in sporadic adenomas. In addition, one of the tumors expressed a cryptic CTNNB1-PLAG1 fusion transcript. Our findings strongly suggest that identical or very similar molecular mechanisms are operating during adenoma tumorigenesis irrespective of whether the tumors are cytogenetically polyclonal or whether they have non-random, tumor specific abnormalities. Cytogenetically polyclonal adenomas are thus most likely also of monoclonal origin.
Enlund
Frederik
F
The Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Goteborg, Sweden.
Nordkvist
Anders
A
Sahlin
Pelle
P
Mark
Joachim
J
Stenman
Göran
G
D008949:Adenoma, Pleomorphic / Q000235:genetics* / Q000532:radiotherapy; D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C104382:PLAG1 protein, human; D015534:Trans-Activators; D051176:beta Catenin; D012313:RNA