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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-11-3456.

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Submitted November 15, 2002
Accepted December 23, 2002

Molecular heterogeneity in MCL, defined by the use of specific VH genes and the frequency of somatic mutations

Francisca I Camacho, Patrocinio Algara, Antonia Rodriguez, Elena Ruiz-Ballesteros, Manuela Mollejo, Nerea Martinez, Jose A Martinez-Climent, Marcos Gonzalez, Marisol Mateo, Alessia Caleo, Margarita Sanchez-Beato, Javier Menarguez, Javier Garcia-Conde, Francesc Sole, Elias Campo, and Miguel A Piris*

Molecular Pathology Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain
Department of Genetics and Pathology, Hospital Virgen de la Salud, Toledo, Spain
Department of Haematology, Hospital Clinico, Valencia, Spain
Department of Haematology, Hospital Clinico, Salamanca, Spain
Laboratory of Citologia Hematologica, Hospital del Mar, Barcelona, Spain
Department of Pathology, Hospital Clinic, Barcelona, Spain
Department of Pathology, Hospital Gregorio Maranon, Madrid, Spain

* Corresponding author; email: mapiris{at}cnio.es.

This study aimed to explores whether the presence of somatic mutations, or a biased use of IgVH genes were associated related with the clinical features in a series of 96 cases of Mantle Cell Lymphoma (MCL). The cases were studied by semi-nested PCR using primers from the FR1 and JH regions. There was results showed an unexpectedly high frequency of somatic mutations, with 29/103 sequences showing more than 2% of mutations. Additionally a bBiased usage of specific VH segments was also found:identified. Thus, the most more widely used genes used in this series were VH3-21 (10 cases), VH3-23 (9), VH4-34 (11) and VH4-59 (9). VH mutational frequency, taking into account different thresholds, did not discriminatetinguishd among different OS overall survival probabilities. Nevertheless, a more frequent use of VH3-21 or VH4-59 (8/18) was observed in the group of long-term survivors (18 cases > 5 yearsrs) (p<0.01). None of these long-term survivors cases presented the VH3-23 gene rearrangement. As in other lymphoproliferative disorders, the expression of CD38 and/or p53 was associated with a worse poorer survival probability. This unon-random usage of IgVH segments suggests that specific antigens may could play a pathogenically relevant role in the genesis or progression of subsets of MCL cases, and may help in distinguishing a significant group of MCL long-term survivors.


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