Delineation of distinct tumour profiles in mantle cell lymphoma by detailed cytogenetic, interphase genetic and morphological analysis.
Mantle cell lymphoma (MCL) is an aggressive lymphoid tumour characterized by the translocation t(11;14)(q13;q32) and a poor clinical outcome (median survival: 3-4 years). Recent studies revealed that increased proliferation of the tumour cells and certain chromosomal aberrations, such as deletions of 17p13 and 9p21 represent major adverse biological markers in this disease, although the molecular targets of chromosomal imbalances in MCL have not been identified for the large majority of loci affected. To correlate histomorphological and proliferation features of MCL with genetic findings, we investigated 223 MCL by fluorescence in situ hybridization (FISH) (n = 157) and/or classical cytogenetic banding analysis (n = 129). FISH analysis turned out to be distinctly more sensitive in the delineation of aberrations. Complex karyotypic alterations were associated with higher proliferation indices and inferior prognosis. A comprehensive analysis of biological features including genetic alterations in MCL by hierarchical clustering resulted in the delineation of four tumour subgroups differing with respect to their genetic constitution and suggesting different transformation or progression pathways. Moreover, in one of the groups identified, a more indolent clinical behaviour was associated with few secondary aberrations and fewer known high-risk chromosomal aberrations, which points to the importance of the quality of karyotypic evolution in MCL tumours.
Department of Pathology, University of Würzburg, Germany.
Tiemo
T
Katzenberger
Dirk
D
Kienle
Stephan
S
Stilgenbauer
Sylvia
S
Höller
Carolin
C
Schilling
Uwe
U
Mäder
Bernhard
B
Puppe
Celine
C
Petzoldt
Sandrine
S
Sander
Lars
L
Bullinger
Heike
H
Stöcklein
Jörg
J
Kalla
Elena
E
Hartmann
Patrick
P
Adam
M Michaela
MM
Ott
Hans-Konrad
HK
Müller-Hermelink
Andreas
A
Rosenwald
German
G
Ott
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D003582:Cytogenetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53