|
|
Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2922-2929
Variable heavy chain gene analysis of follicular lymphomas:
correlation between heavy chain isotype expression and somatic mutation
load
Wilhelmina M. Aarts,
Richard J. Bende,
Eric J. Steenbergen,
Philip M. Kluin,
Engelbert C. M. Ooms,
Steven T. Pals, and
Carel J. M. van
Noesel
From the Department of Pathology, Academic Medical Center,
Amsterdam; the Department of Pathology, Radboud Hospital, Nijmegen; the
Department of Pathology, Leiden University Medical Center, Leiden; and
the Department of Pathology, the Westeinde Hospital, The Hague, the
Netherlands.
The expansion of follicular lymphomas (FLs) resembles, both
morphologically and functionally, normal germinal center B-cell growth.
The tumor cells proliferate in networks of follicular dendritic cells
and are believed to be capable of somatic hypermutation and isotype
switching. To investigate the relation between somatic mutation and
heavy chain isotype expression, we analyzed the variable heavy
(VH) chain genes of 30 FL samples of different
isotypes. The VH genes of the FLs were heavily mutated
(29.3 mutations on average). In addition, isotype-switched lymphomas
contained more somatic mutations than immunoglobulin M-positive
lymphomas (33.8 mutations per VH gene versus 23.0, respectively). In all but one of the FLs, the ratios of replacement
versus silent mutations in the framework regions were low, independent
of the absolute number of somatic mutations and the level of
intraclonal variation. Analysis of relapse samples of 4 FLs showed no
obvious increase in somatic mutation load in most FLs and a decrease in
intraclonal variation in time. In 3 of 4 cases, we obtained evidence
for selection of certain subclones, rather than clonal evolution. Our
findings question if intraclonal variation is always a reflection of
ongoing somatic hypermutation. This may have implications for the
concept of antigen-driven lymphomagenesis.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
J. Agopian, J.-M. Navarro, A.-C. Gac, Y. Lecluse, M. Briand, P. Grenot, P. Gauduchon, P. Ruminy, P. Lebailly, B. Nadel, et al.
Agricultural pesticide exposure and the molecular connection to lymphomagenesis
J. Exp. Med.,
July 6, 2009;
206(7):
1473 - 1483.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Carlotti, D. Wrench, J. Matthews, S. Iqbal, A. Davies, A. Norton, J. Hart, R. Lai, S. Montoto, J. G. Gribben, et al.
Transformation of follicular lymphoma to diffuse large B-cell lymphoma may occur by divergent evolution from a common progenitor cell or by direct evolution from the follicular lymphoma clone
Blood,
April 9, 2009;
113(15):
3553 - 3557.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R B Ilgenfritz, K Kayasut, A Le Tourneau, O A Calendini, L Ouafi, C Marzac, J Diebold, F Devez, V Ducruit, P E Bouchet, et al.
Correlation between molecular and histopathological diagnoses of B cell lymphomas in bone marrow biopsy and aspirates
J. Clin. Pathol.,
April 1, 2009;
62(4):
357 - 360.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Ruminy, F. Jardin, J.-M. Picquenot, F. Parmentier, N. Contentin, G. Buchonnet, S. Tison, V. Rainville, H. Tilly, and C. Bastard
S{micro} mutation patterns suggest different progression pathways in follicular lymphoma: early direct or late from FL progenitor cells
Blood,
September 1, 2008;
112(5):
1951 - 1959.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y Sato, K Ichimura, T Tanaka, K Takata, T Morito, H Sato, E Kondo, H Yanai, N Ohara, T Oka, et al.
Duodenal follicular lymphomas share common characteristics with mucosa-associated lymphoid tissue lymphomas
J. Clin. Pathol.,
March 1, 2008;
61(3):
377 - 381.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. J. Bende, F. van Maldegem, M. Triesscheijn, T. A.M. Wormhoudt, R. Guijt, and C. J.M. van Noesel
Germinal centers in human lymph nodes contain reactivated memory B cells
J. Exp. Med.,
October 29, 2007;
204(11):
2655 - 2665.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Sansonno, A. Carbone, V. De Re, and F. Dammacco
Hepatitis C virus infection, cryoglobulinaemia, and beyond
Rheumatology,
April 1, 2007;
46(4):
572 - 578.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A Mottok, M-L Hansmann, and A Brauninger
Activation induced cytidine deaminase expression in lymphocyte predominant Hodgkin lymphoma
J. Clin. Pathol.,
September 1, 2005;
58(9):
1002 - 1004.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. J. Bende, W. M. Aarts, R. G. Riedl, D. de Jong, S. T. Pals, and C. J.M. van Noesel
Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity
J. Exp. Med.,
April 18, 2005;
201(8):
1229 - 1241.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. A. Smit, R. J. Bende, J. Aten, J. E. J. Guikema, W. M. Aarts, and C. J. M. van Noesel
Expression of Activation-induced Cytidine Deaminase Is Confined to B-Cell Non-Hodgkin's Lymphomas of Germinal-Center Phenotype
Cancer Res.,
July 15, 2003;
63(14):
3894 - 3898.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. J. Bende, L. A. Smit, J. G. Bossenbroek, W. M. Aarts, M. Spaargaren, L. de Leval, G. E. E. Boeckxstaens, S. T. Pals, and C. J. M. van Noesel
Primary Follicular Lymphoma of the Small Intestine: {alpha}4{beta}7 Expression and Immunoglobulin Configuration Suggest an Origin from Local Antigen-Experienced B Cells
Am. J. Pathol.,
January 1, 2003;
162(1):
105 - 113.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Oeschger, A. Brauninger, R. Kuppers, and M.-L. Hansmann
Tumor cell dissemination in follicular lymphoma
Blood,
March 15, 2002;
99(6):
2192 - 2198.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. M. Aarts, R. J. Bende, J.-W. Vaandrager, P. M. Kluin, A. W. Langerak, S. T. Pals, and C. J.M. van Noesel
In Situ Analysis of the Variable Heavy Chain Gene of an IgM/IgG-Expressing Follicular Lymphoma : Evidence for Interfollicular Trafficking of Tumor Cells
Am. J. Pathol.,
March 1, 2002;
160(3):
883 - 891.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. L. Fenton, J.-W. Vaandrager, W. M. Aarts, R. J. Bende, K. Heering, M. van Dijk, G. Morgan, C. J. M. van Noesel, E. Schuuring, and P. M. Kluin
Follicular lymphoma with a novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells
Blood,
January 15, 2002;
99(2):
716 - 718.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. M. Aarts, R. J. Bende, J. G. Bossenbroek, S. T. Pals, and C. J. M. van Noesel
Variable heavy-chain gene analysis of follicular lymphomas: subclone selection rather than clonal evolution over time
Blood,
July 1, 2001;
98(1):
238 - 240.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Welzel, T. Le, R. Marculescu, G. Mitterbauer, A. Chott, C. Pott, M. Kneba, M.-Q. Du, R. Kusec, J. Drach, et al.
Templated Nucleotide Addition and Immunoglobulin JH-Gene Utilization in t(11;14) Junctions: Implications for the Mechanism of Translocation and the Origin of Mantle Cell Lymphoma
Cancer Res.,
February 1, 2001;
61(4):
1629 - 1636.
[Abstract]
[Full Text]
|
 |
|
|
|