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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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Blood, 15 May 2003, Vol. 101, No. 10, pp. 4042-4046
NEOPLASIA
Molecular heterogeneity in MCL defined by the use of specific
VH genes and the frequency of somatic
mutations
Francisca I. Camacho,
Patrocinio Algara,
Antonia Rodríguez,
Elena Ruíz-Ballesteros,
Manuela Mollejo,
Nerea Martínez,
José A. Martínez-Climent,
Marcos González,
Marisol Mateo,
Alessia Caleo,
Margarita Sánchez-Beato,
J. Menárguez,
Javier García-Conde,
Francesc Solé,
Elías Campo, and
Miguel A. Piris
From the Centro Nacional de Investigaciones
Oncológicas (CNIO), Molecular Pathology Program, Madrid,
Spain; Department of Genetics and Pathology, Hospital
Virgen de la Salud, Toledo, Spain; Department of
Hematology and Medical Oncology, Hospital Clínico, University
of Valencia, Valencia, Spain; Department of Hematology,
Hospital Clínico, Salamanca, Spain; Laboratory of
Citología Hematológica, Department of Pathology, Hospital
del Mar, Barcelona, Spain; Department of Pathology,
Hospital Clinic, Barcelona, Spain; and Department of
Pathology, Hospital Gregorio Marañón, Madrid,
Spain.
This study explores whether the presence of somatic mutations or a
biased use of IgVH genes were
associated with the clinical features in a series of 96 patients with
mantle cell lymphoma (MCL). The cases were studied by seminested
polymerase chain reaction using primers from the FR1 and JH
regions. There was an unexpectedly high frequency of somatic mutations,
with 29 of 103 sequences showing more than 2% of mutations. Biased usage of specific VH segments was also found;
the most widely used genes in this series were
VH3-21 (10 cases),
VH3-23 (9 cases),
VH4-34 (11 cases), and
VH4-59 (9 cases).
VH mutation frequency, taking into account
different thresholds, did not distinguish different overall survival
probabilities. Nevertheless, a more frequent use of
VH3-21 or VH4-59 (8 of
18) was observed in the group of long-term survivors (18 cases > 5 years; P < .01). None of these long-term survivors
presented the VH3-23 gene rearrangement. As in
other lymphoproliferative disorders, the expression of CD38 or p53 or
both was associated with a poorer survival probability. This nonrandom
usage of IgVH segments suggests that specific
antigens may 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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