High Proliferation Rate in Mantle Cell Lymphoma is Associated with p53 Mutations and Blastoid Morphology, but Not with 3'UTR Deficient Cyclin D1 mRNA or High Total Cyclin D1 mRNA Levels [1298]

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Version: author
Serval ID
serval:BIB_F8F06EA49591
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Title
High Proliferation Rate in Mantle Cell Lymphoma is Associated with p53 Mutations and Blastoid Morphology, but Not with 3'UTR Deficient Cyclin D1 mRNA or High Total Cyclin D1 mRNA Levels [1298]
Title of the conference
Annual Meeting of the United States and Canadian Academy of Pathology
Author(s)
Slotta-Huspenina J., Koch I., De Leval L., Keller G., Bink K., Kremer M., Raffeld M., Fend F., Quintanilla-Martinez L.
Address
Boston, United States, 2009, March, 7-13
ISBN
0893-3952
ISSN-L
0893-3952
Publication state
Published
Issued date
2009
Volume
22
Series
Modern Pathology
Pages
287A
Language
english
Abstract
Background: The hallmark of MCL is overexpression of cyclin D1 (CyD1).
Predominance of 3'UTR-deficient CyD1 mRNA and genomic 3'UTR alteration were
found to be associated with a "proliferation signature" and poor prognosis. The aim
of our study was to correlate the expression of CyD1 mRNA isoforms and genomic
3'UTR alterations, as well as secondary genetic alterations (p53, p16 and c-myc) with
morphology and proliferation rate, as measured by MIB 1 staining in primary MCL.
Design: Paraffin-embedded tissue of 62 CyD1+MCL (10 blastoid and 52 typical)
were analysed for expression of CyD1 3'UTR isoforms and genomic 3'UTR
deletion by real-time RT-PCR and genomic qPCR, respectively. Findings were
correlated with morphology and proliferation rate (MIB 1 pos <10%, 11-30%,
>30%). P53 overexpression, as surrogate marker for p53 mutations was assessed by
immunohistochemistry (>20%) and confirmed by DHPLC and sequencing analysis.
P16 deletions and c-myc gene alterations were analysed by FISH.
Results: Predominance of CyD1 3'UTR deficient mRNA was found in 14 (22.6%)
samples, including 4 with complete loss of the standard transcript, accompanied by
genomic UTR deletion in two cases. P53 overexpression/ mutation was found in 12
cases. 3'UTR predominance was significantly associated with high total CyD1 mRNA
levels (mean CyD1/TBP 87.2 vs 62.1, p=0.01) and blastoid morphology (5/10, p=0.04),
but not with high proliferation rate (6/18, p=0.32). Instead, high proliferation rate
(>30%) was significantly correlated with blastoid morphology (9/10, p<0.001) and
p53 overexpression (11/12, p<0.001). In five highly proliferative cases without p53
mutations other secondary genetic alterations were investigated. In none of the cases
p16 deletions or c-myc translocations were identified.
Conclusions: Predominance of the 3'UTR CyD1 deficient mRNA and CyD1 3'UTR
deletion in MCL is associated with high total CyD1 mRNA level and blastoid
morphology but not with high proliferation rate, as assessed by MIB 1 staining. In
contrast, proliferation rate is highly associated with blastoid morphology and p53
overexpression.
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