RESUMEN
AIMS: Leiomyosarcomas (LMSs) occur in various tissues and harbour potential for metastases. The genomic landscape of LMS is poorly understood. In an effort to improve understanding of the LMS genome, we analysed 11 LMSs of somatic soft tissue including matching tissue of normal phenotype. METHODS: DNA derived from microdissected tumour domains and matching normal tissue underwent amplicon sequencing of 409 tumour suppressors and oncogenes using the Ion Torrent Comprehensive Cancer Panel. RESULTS: Genomic changes were heterogeneous with few recurrent abnormalities detected. Coding variants were identified in genes involved in signal transduction, transcriptional regulation and DNA repair. There were variants in several genes related to angiogenesis and GPR124 variants (TEM5) were confirmed by immunohistochemical analysis of a LMS tissue microarray. Surprisingly, there were shared coding variants in tumour and corresponding normal tissue. CONCLUSIONS: LMSs are a very heterogeneous population lacking recurrent somatic abnormalities. The presence of damaging mutations in normal tissue may reflect either a germline predisposition or field effect rather than tissue contamination. Hopeful therapeutic targets appear to be those related to AKT/MTOR pathway.
Asunto(s)
Biomarcadores de Tumor/genética , Análisis Mutacional de ADN/métodos , Dosificación de Gen , Leiomiosarcoma/genética , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Neoplasias de los Tejidos Blandos/genética , Biomarcadores de Tumor/análisis , Variaciones en el Número de Copia de ADN , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Leiomiosarcoma/química , Leiomiosarcoma/patología , Leiomiosarcoma/terapia , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias de los Tejidos Blandos/química , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapiaRESUMEN
OBJECTIVE: The aim of this study was to measure spontaneous photon emission (SPE) and delayed luminescence (DL) from various human cancer tissues. MATERIALS AND METHODS: A photomultiplier tube attached to a dark chamber was used for the detection of ultraweak photon emission from cancer tissues in the chamber. The samples were illuminated with a 150 W metal halide lamp for the measurement of delayed luminescence. Frozen tissues were provided by the hospitals and preserved in saline solution in a CO2 incubator for 1 hour before starting the measurement of spontaneous photon emission. We successively measured the afterglows from the samples after 30-second irradiation of the lamp. The samples were divided into two groups: tumor tissues and normal tissues around tumor tissues. We presented experimental data and interpreted their characteristic patterns of spontaneous photon emission and delayed luminescence. RESULTS: Mean values of spontaneous photon emissions from the normal tissues and the tumor tissues were measured with the standard errors of the mean as 625 +/- 419 counts/minute/cm2 (n = 6) and 982 +/- 513 counts/minute/cm2 (n = 14), respectively. Peak values of the intensity of delayed luminescence from normal and cancerous tissues were 63 +/- 20 counts/ms (n = 6) and 48 +/- 12 counts/ms (n = 14). CONCLUSIONS: The intensity of spontaneous photon emissions from cancer tissues were mostly discriminated from those of normal tissues, and their delayed luminescent properties were investigated.