RESUMEN
The Montecristo district, northern Chile, is one of the few places worldwide where there is a direct relationship between magnetite-(apatite) (MtAp) mineralization and iron oxide-copper-gold (IOCG) mineralization. The MtAp mineralization includes Ti-poor magnetite, fluorapatite, and actinolite and is crosscut and partially replaced by a younger IOCG mineralization that includes a second generation of actinolite and magnetite with quartz, chalcopyrite, pyrite, and molybdenite. The MtAp stage at Montecristo is interpreted as the crystallized iron-rich melts that used the pre-existing structures of the Atacama Fault System as conduits. These rocks later acted as a trap for hydrothermal IOCG mineralization. Geochronology data at Montecristo indicate that the host diorite (U-Pb zircon 153.3 ± 1.8 Ma, 2-sigma), MtAp mineralization (40Ar-39Ar in actinolite, 154 ± 2 Ma and 153 ± 4 Ma, 2-sigma), and the IOCG event (Re-Os on molybdenite, 151.8 ± 0.6 Ma, 2-sigma) are coeval within error and took place in a time span of less than 3.4 Ma. The εHfi and εNdi values of the host diorite are + 8.0 to + 9.8 and + 4.3 to + 5.4, respectively. The whole-rock 87Sr/86Sri values of the IOCG mineralization (0.70425 to 0.70442) are in the lower end of those of the MtAp mineralization (0.70426-0.70629). In contrast, εNdi values for the IOCG mineralization (+ 5.4 and + 5.7) fall between those of the MtAp rocks (+ 6.6 to + 7.2) and the host diorite, which suggests that the IOCG event was related to fluids having a more crustal Nd (εNdi < + 5.7) composition than the MtAp mineralization. This likely reflects the mixing of Nd from the MtAp protolith and a deep magmatic-hydrothermal source, very likely an unexposed intrusion equivalent to the host diorite. Sulfur isotope compositions (δ34S, + 0.3 to + 3.4) are consistent with a magmatic source. Supplementary Information: The online version contains supplementary material available at 10.1007/s00126-023-01172-0.
RESUMEN
Pilocytic astrocytoma (PA) is the most frequent solid neoplasm in childhood. It has a good 5-year overall survival (90% in childhood and 52% in adults). However, up to 20% of patients experience residual tumor growth, recurrence, and death. Although the main genetic alteration of PAs, including KIAA1549:BRAF fusion, involves chromosome 7q34, we previously found frequent loss in chr9q34.3 locus in a small subset of these tumors. Among the genes present in this locus, EGFL7 is related to poor prognosis in several tumor types. In this study, we aimed to assess EGFL7 expression through immunohistochemistry, and to evaluate its prognostic value in a series of 64 clinically and molecularly well-characterized pilocytic astrocytomas. We found high expression of EGFL7 in 71.9% of patients. Low EGFL7 expression was associated with older patients, the mean age mainly older than 11 years (P = 0.027). EGFL7 expression was not associated with presence of KIAA1549:BRAF fusion, BRAF mutation, FGFR1 mutation, nor FGFR1 duplication. Moreover, high EGFL7 expression was associated with high FGFR1 (P = 0.037) and 5'-deoxy-5'-methyltioadenosine phosphorylase (MTAP) (P = 0.005) expression, and with unfavorable outcome of patients (P = 0.047). Multivariate analysis revealed low EGFL7 expression related to older patients and high EGFL7 expression related to retained expression of MTAP. In addition, we found a borderline significance of unfavorable outcome and high EGFL7 expression. Finally, EGFL7 expression was not associated with overall or event-free survival of PA patients. Our findings point to EGFL7 expression as a novel candidate prognostic marker in PA, which should be further investigated.
Asunto(s)
Astrocitoma/diagnóstico , Astrocitoma/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Proteínas de Unión al Calcio/biosíntesis , Familia de Proteínas EGF/biosíntesis , Adolescente , Adulto , Astrocitoma/genética , Neoplasias Encefálicas/genética , Proteínas de Unión al Calcio/genética , Niño , Preescolar , Familia de Proteínas EGF/genética , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación/genética , Pronóstico , Adulto JovenRESUMEN
The 5'-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients' clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients' clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP's role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.
Asunto(s)
Neoplasias Encefálicas/enzimología , Neoplasias Encefálicas/genética , Glioma/enzimología , Glioma/genética , Purina-Nucleósido Fosforilasa/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Niño , Preescolar , Femenino , Edición Génica , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica/genética , Pronóstico , Purina-Nucleósido Fosforilasa/genética , Transfección , Adulto JovenRESUMEN
AIM: The Ewing sarcoma family of tumors (ESFT) is a group of malignant small round cell neoplasms of bones and soft tissues closely histogenetically related. Methylthioadenosine phosphorylase (MTAP) deficiency has been recently associated with increased tumor aggressiveness and poor outcomes in different types of neoplasms. However, the expression of this biomarker and its biological role in ESFT remain largely unknown. METHODS: Immunohistochemical expression of MTAP was accessed in 112 patients with ESFT in a tissue microarray platform and associated with clinicopathological parameters and overall survival (OS). RESULTS: Loss of MTAP expression was significantly associated with lower OS in both univariate and multivariate analyses. CONCLUSION: Loss of MTAP expression is an independent negative prognostic biomarker in ESFT.