Asunto(s)
Metilación de ADN/genética , Eliminación de Gen , Péptidos y Proteínas de Señalización Intracelular/genética , Linfoma de Células B de la Zona Marginal/genética , Mutación/genética , Proteínas Nucleares/genética , Regiones Promotoras Genéticas/genética , Adulto , Anciano , Anciano de 80 o más Años , Niño , Proteínas de Unión al ADN , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/patología , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfaRESUMEN
The genetic basis of MALT lymphoma is largely unknown. Characteristic chromosomal translocations are frequently associated with gastric and pulmonary cases, but are rare at other sites. We compared the genetic profiles of 33 ocular adnexal and 25 pulmonary MALT lymphomas by 1 Mb array-comparative genomic hybridization (CGH) and revealed recurrent 6q23 losses and 6p21.2-6p22.1 gains exclusive to ocular cases. High-resolution chromosome 6 tile-path array-CGH identified NF-kappaB inhibitor A20 as the target of 6q23.3 deletion and TNFA/B/C locus as a putative target of 6p21.2-22.1 gain. Interphase fluorescence in situ hybridization showed that A20 deletion occurred in MALT lymphoma of the ocular adnexa (8/42=19%), salivary gland (2/24=8%), thyroid (1/9=11%) and liver (1/2), but not in the lung (26), stomach (45) and skin (13). Homozygous deletion was observed in three cases. A20 deletion and TNFA/B/C gain were significantly associated (p<0.001) and exclusively found in cases without characteristic translocation. In ocular cases, A20 deletion was associated with concurrent involvement of different adnexal tissues or extraocular sites at diagnosis (p=0.007), a higher proportion of relapse (67% versus 37%) and a shorter relapse-free survival (p=0.033). A20 deletion and gain at TNFA/B/C locus may thus play an important role in the development of translocation-negative MALT lymphoma.
Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/genética , Linfoma de Células B de la Zona Marginal/genética , Proteínas Nucleares/genética , Neoplasias Orbitales/genética , Neoplasias de las Glándulas Salivales/genética , Factor de Necrosis Tumoral alfa/genética , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Cromosomas Humanos Par 6 , Hibridación Genómica Comparativa/métodos , Proteínas de Unión al ADN , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Hibridación Fluorescente in Situ , Interfase , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Eliminación de Secuencia , Neoplasias Cutáneas/genética , Neoplasias Gástricas/genética , Neoplasias de la Tiroides/genética , Translocación Genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfaRESUMEN
Chlamydia pneumoniae, Chlamydia trachomatis and Chlamydia psittaci were detected at low frequencies (<20%) among 69 pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas, 30 other lymphoproliferative disorders (LPD) and 44 non-LPD. The incidence of individual Chlamydiae was generally higher in MALT lymphoma than non-LPD, although not reaching statistical significance. Mycoplasma pneumoniae DNA was not detected.
Asunto(s)
Infecciones por Chlamydia/diagnóstico , Linfoma de Células B de la Zona Marginal/microbiología , Infecciones por Mycoplasma/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Chlamydia trachomatis/aislamiento & purificación , Chlamydophila pneumoniae/aislamiento & purificación , Chlamydophila psittaci/aislamiento & purificación , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/complicaciones , Trastornos Linfoproliferativos/microbiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Infectious agents play a critical role in MALT lymphoma development. Studies from Italy showed Chlamydia psittaci infection in 87% of ocular adnexal MALT lymphomas and complete or partial regression of the lymphoma after C. psittaci eradication in four of nine cases. However, C. psittaci was not demonstrated in ocular adnexal MALT lymphomas from the USA. This study was thus designed to investigate further the role of C. psittaci, and other infectious agents commonly associated with chronic eye disease, in the development of ocular adnexal MALT lymphoma. The presence of C. psittaci, C. trachomatis, C. pneumoniae, herpes simplex virus 1 and 2 (HSV1, HSV2), and adenovirus 8 and 19 (ADV8, ADV19) was assessed separately by polymerase chain reaction in 142 ocular adnexal MALT lymphomas, 53 non-marginal zone lymphomas, and 51 ocular adnexal biopsies without a lymphoproliferative disorder (LPD), from six geographical regions. C. psittaci was detected at similar low frequencies in non-LPD and non-marginal zone lymphoma groups from different geographical regions (0-14%). Overall, the prevalence of C. psittaci was significantly higher in MALT lymphomas (22%) than in non-LPD (10%, p=0.042) and non-marginal zone lymphoma cases (9%, p=0.033). However, the prevalence of C. psittaci infection in MALT lymphoma showed marked variation among the six geographical regions examined, being most frequent in Germany (47%), followed by the East Coast of the USA (35%) and the Netherlands (29%), but relatively low in Italy (13%), the UK (12%), and Southern China (11%). No significant differences in the detection of C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were found between lymphomas and controls from different geographical regions. In conclusion, our results show that C. psittaci, but not C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8 or ADV19, is associated with ocular adnexal MALT lymphoma and that this association is variable in different geographical areas.