RESUMEN
Giant cell tumor of bone (GCTB) is characterized cytogenetically by frequent telomeric associations (tas). To explore the mechanisms behind the formation of tas in GCTB and to investigate their karyotypic consequences, the frequencies of tas and clonal aberrations other than tas in 20 GCTBs were compared to telomere length and status, as assessed by quantitative PCR, fluorescence in situ hybridization (FISH), and expression levels of four genes involved in telomere maintenance. Based on the G-banding results, the tumors were divided into two groups, one with a high frequency of tas and one with a low frequency. Clonal aberrations were found to be restricted to the group with a high level of tas, and the same group showed a significantly larger reduction in telomere length in tumor cells compared to peripheral blood cells. Furthermore, 65 out of 66 tas analyzed by FISH were negative for telomeric sequences. The expression levels of TERT, TERF1, TERF2, and POT1 did not correlate with telomere length or the frequency of tas. Thus, the present findings provide strong support for the notion that decreased telomere length is a prerequisite for tas in GCTBs and that the clonal changes occurring in GCTBs are derived from tas.
Asunto(s)
Aberraciones Cromosómicas , Tumor Óseo de Células Gigantes/genética , Telómero/metabolismo , Adolescente , Adulto , Bandeo Cromosómico , Células Clonales , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Complejo Shelterina , Telomerasa/genética , Telomerasa/metabolismo , Proteínas de Unión a Telómeros/genética , Proteínas de Unión a Telómeros/metabolismo , Proteína 2 de Unión a Repeticiones Teloméricas/genética , Proteína 2 de Unión a Repeticiones Teloméricas/metabolismoRESUMEN
We reviewed nine patients at a mean period of 11 years (6 to 16) after curettage and cementing of a giant-cell tumour around the knee to determine if there were any long-term adverse effects on the cartilage. Plain radiography, MRI, delayed gadolinium-enhanced MRI of the cartilage and measurement of the serum level of cartilage oligomeric matrix protein were carried out. The functional outcome was evaluated using the Lysholm knee score. Each patient was physically active and had returned to their previous occupation. Most participated in recreational sports or exercise. The mean Lysholm knee score was 92 (83 to 100). Only one patient was found to have cartilage damage adjacent to the cement. This patient had a history of intra-articular fracture and local recurrence, leading to degenerative changes. Interpretation of the data obtained from delayed gadolinium-enhanced MRI of the cartilage was difficult, with variation in the T1 values which did not correlate with the clinical or radiological findings. We did not find it helpful in the early diagnosis of degeneration of cartilage. We also found no obvious correlation between the serum cartilage oligomeric matrix protein level and the radiological and MR findings, function, time after surgery and the age of the patient. In summary, we found no evidence that the long-term presence of cement close to the knee joint was associated with the development of degenerative osteoarthritis.
