Deregulated expression of the polycomb-group protein SUZ12 target genes characterizes mantle cell lymphoma.
Polycomb proteins are known to be of great importance in human cancer pathogenesis. SUZ12 is a component of the Polycomb PRC2 complex that, along with EZH2, is involved in embryonic stem cell differentiation. EZH2 plays an essential role in many cancer types, but an equivalent involvement of SUZ12 has not been as thoroughly demonstrated. Here we show that SUZ12 is anomalously expressed in human primary tumors, especially in mantle cell lymphoma (MCL), pulmonary carcinomas and melanoma, and is associated with gene locus amplification in some cases. Using MCL as a model, functional and genomic studies demonstrate that SUZ12 loss compromises cell viability, increases apoptosis, and targets genes involved in central oncogenic pathways associated with MCL pathogenesis. Our results support the hypothesis that the abnormal expression of SUZ12 accounts for some of the unexplained features of MCL, such as abnormal DNA repair and increased resistance to apoptosis.
Martín-Pérez
Daniel
D
Lymphoma Group, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.
Sánchez
Esther
E
Maestre
Lorena
L
Suela
Javier
J
Vargiu
Pierfrancesco
P
Di Lisio
Lorena
L
Martínez
Nerea
N
Alves
Javier
J
Piris
Miguel A
MA
Sánchez-Beato
Margarita
M
D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D004260:DNA Repair; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D063151:Polycomb Repressive Complex 2; D014157:Transcription Factors
D002352:Carrier Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C430461:SUZ12 protein, human; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2