RESUMEN
Gastric extranodal marginal zone lymphoma (EMZL) often shows prolonged localised disease, but the present study demonstrated the presence of tumour cells in peripheral blood (PB) of low stage patients. We studied the presence of tumour cells in PB in gastric lymphoma patients harbouring or lacking t(11;18)(q21;q21), by real-time immunoglobulin (Ig)H allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) and API2-MALT1 PCR. Tumour cells were exclusively detected in PB of t(11;18)(q21;q21)+-EMZL patients. The presence of tumour cells in PB and gastric biopsy follow-up samples showed a good correlation in these patients, suggesting clinical relevance for monitoring of tumour cells in PB of gastric t(11;18)(q21;q21)+-EMZL patients.
Asunto(s)
Cadenas Pesadas de Inmunoglobulina/genética , Linfoma de Células B de la Zona Marginal/patología , Neoplasia Residual/patología , Células Neoplásicas Circulantes/patología , Neoplasias Gástricas/patología , Adulto , Anciano , Alelos , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 18 , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/genética , Translocación GenéticaRESUMEN
Primary cutaneous marginal zone lymphomas (PCMZL) share histological and clinical characteristics with mucosa-associated lymphoid tissue (MALT) lymphomas suggesting a common pathogenesis. A number of recurrent structural and numerical chromosomal aberrations have been described in MALT lymphoma, but their incidence in PCMZL is largely unknown, as is their relation with clinical and pathological data. In this study, the incidence of t(11;18)(q21;q21), t(1;14)(p22;q32), two different t(14;18)(q32;q21), involving either IGH/MALT1 or IGH/BCL2, and numerical aberrations of chromosomes 3, 7, 12 and 18 were analysed in 12 patients with PCMZL, with follow-up of up to 10 years. Nuclei were isolated from paraffin wax sections for dual-colour interphase fluorescence in situ hybridization (FISH) using various probe sets either flanking or spanning the involved genes. T(14;18)(q32;q21), with breakpoints in IGH and MALT1, was found in three cases. All three had partly monocytoid histological appearances and lacked blastic transformation. An additional trisomy of chromosome 3 was detected in one of these cases. Trisomy 18 was present in two lymphomas without monocytoid morphology. No definite correlation was seen with any clinical feature, including Borrelia serology. Neither t(11;18)(q21;q21), nor t(1;14)(p22;q32) or any other translocation involving IGH, BCL10, MALT1, BCL2 and API2, amplification or deletion of chromosomal region 11q21, 18q21, 1p22, and 14q32 was detected. These results indicate that a subgroup of PCMZL with partly monocytoid morphology is genetically related to MZL at other extranodal sites.
Asunto(s)
Linfoma de Células B/genética , Neoplasias Cutáneas/genética , Translocación Genética , Trisomía , Adulto , Anciano , Anciano de 80 o más Años , Caspasas , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 18/genética , Femenino , Estudios de Seguimiento , Humanos , Hibridación Fluorescente in Situ , Linfoma de Células B/patología , Linfoma de Células B de la Zona Marginal/genética , Masculino , Persona de Mediana Edad , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Proteínas de Neoplasias/genética , Pronóstico , Neoplasias Cutáneas/patologíaRESUMEN
Using immunoelectron microscopy it is demonstrated that desmin subunits missing their complete carboxy-terminal domain are incapable of homopolymeric filament formation in vivo. Furthermore it is shown that, in vimentin-containing cells, desmin integrates into preexisting vimentin filaments resulting in desmin/vimentin heteropolymers. Removal of the amino-terminal or both nonhelical end domains of desmin increases Triton X-100 solubility of the mutant desmin subunits. Expression of desmin mutants containing deletions in the C-terminal part of the rod in vimentin-free cells results in an increase of the Triton X-100 solubility too. In contrast, if expressed in vimentin-containing cells, these mutant subunits remain in the Triton X-100 insoluble fraction. Deletion of the nonhelical carboxy-terminal domain only has no effect on solubility. In vimentin-free cells, stably expressed desmin subunits missing their amino-terminal domains display a slightly higher turnover rate compared to wild-type desmin. Transiently expressed desmin subunits missing 18 or more carboxy-terminal residues of the rod domain are rapidly degraded in vimentin-free cells. In vimentin-containing cells, turnover rates were much less pronounced. Finally, by using site-directed mutagenesis, we were able to map specific residues important for de novo filament assembly within the amino-terminal domain and in the conserved part at the C-terminus of the alpha-helical domain.
