Microsatellite instability analysis in tumors with different mechanisms for total loss of HLA expression |
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Authors: | P Jimenez J Cantón A Concha T Cabrera M Fernández L M Real A García A Serrano F Garrido F Ruiz-Cabello |
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Institution: | (1) Departamento de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. Fuerzas Armadas sn, E-18012 Granada, Spain e-mail: fruizc@goliat.ugr.es Tel.: +34-958241684, ES;(2) Anatomía Patológica, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain, ES |
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Abstract: | Down-regulation of the expression of major histocompatibility complex molecules is a frequent event that is associated with
the poor immunogenicity of tumor cells. Acquired resistence to T-cell-based immunotherapy has been associated with loss of
functional β2-microglobulin expression. This anomaly appears to be particularly relevant in tumors exhibiting a defect in
DNA-mismatch repair, and induces structural abnormalities in HLA cell-surface expression that are not reversible by cytokine
treatment. We examined HLA expression in 118 melanoma, colon or larynx tumors to identify total loss of HLA class I expression
with or without somatic β2-microglobulin gene mutation. Microsatellite instability was investigated in these tumors to determine
whether a replication error phenotype (RER+) implied a particular alteration in HLA phenotype. A total of 7.6% of the tumors showed the RER+ phenotype, and 12.7% were HLA-ABC-negative. In the RER+ group, only one tumor was HLA-ABC-negative and no β2-microglobulin mutation was identified. In contrast, in the HLA-ABC-negative
group, only one tumor showed microsatellite instability. None of the three melanomas that contained β2-microglobulin mutation
exhibited the mutator phenotype. These findings suggest that β2-microglobulin mutation in human melanoma tumors may arise
through a mechanism that does not necessarily involve microsatellite instability. Our results also indicate that somatic mutations
of the β2-microglobulin gene are not the main mechanism of total loss of HLA expression.
Received: 14 June 1999 / Accepted: 16 September 1999 |
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Keywords: | Microsatellite instability β 2-Microglobulin Loss of heterozygosity |
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