title: Analysis of Aurora-A and hMPS1 mitotic kinases in mantle cell lymphoma.
abstract: Aurora-A and hMPS1 are kinases involved in spindle checkpoint and centrosome duplication regulation and whose alterations have been associated with cell transformation and chromosome instability in different tumor models. In this study, we have examined the possible alterations of these genes in 58 mantle cell lymphomas (MCLs) and 4 MCL-related cell lines. Aurora-A was also examined in 46 diffuse large B-cell lymphomas (DLBCLs). Aurora-A and hMPS1 mRNA expression levels were related to tumor proliferative activity. Interestingly, a MCL case with the highest number or chromosomal imbalances also showed an extremely high value of Aurora-A mRNA expression. No Aurora-A gene amplifications were detected in any tumor or cell line, whereas hemizygous hMPS1 gene deletions were observed in 23% of MCLs and 3 of the 4 cell lines. However, no expression alterations or gene mutations were detected in these cases. The Aurora-A proposed cancer susceptibility polymorphic variant (P31I) was observed with a similar frequency in MCL, DLBCL, chronic lymphocytic leukemia and in the 431 healthy controls. However, the 3 MCLs and 4 DLBCLs with the homozygous variant of this polymorphism had particular clinical characteristics with an unusual early-age presentation and second epithelial malignancies in MCL and extranodal origin in DLBCL. These findings indicate that Aurora-A and hMPS1 aberrations are uncommon in aggressive lymphomas but Aurora-A overexpression may contribute to numerical chromosomal alterations in occasional MCL. Although the Aurora-A P31I polymorphic variant is not directly involved in a genetic predisposition to these lymphomas, it may modulate the clinical presentation of these tumors.
authors.affiliation: Department of Pathology, Hospital Clinic, Institut d'Investigacións Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Camacho
authors.forename: Silvia
authors.initials: S
authors.lastname: Beà
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverría
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Xavier
authors.initials: X
authors.lastname: Puig
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Benavente
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Luis
authors.initials: L
authors.lastname: Hernández
mesh_terms: D064127:Aurora Kinases; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011505:Protein-Tyrosine Kinases; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D011505:Protein-Tyrosine Kinases; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human