Acceleration of the DNA methylation clock among lynch syndrome-associated mutation carriers.

BACKGROUND: DNA methylation (DNAm) age metrics have been widely accepted as an epigenetic biomarker for biological aging and disease. The purpose of this study is to assess whether or not individuals carrying Lynch Syndrome-associated mutations are affected in their rate of biological aging, as measured by the epigenetic clock. METHODS: Genome-wide bisulfite DNA sequencing data were generated using DNA from CD4 + T-cells obtained from peripheral blood using 27 patient samples from Lynch syndrome families. Horvath's DNAm age model based on penalized linear regression was applied to estimate DNAm age from patient samples with distinct clinical and genetic characteristics to investigate cancer mutation-related aging effects. RESULTS: Both Lynch mutation carriers and controls exhibited high variability in their estimated DNAm age, but regression analysis showed steeper slope for the Lynch mutation carriers. Remarkably, six Lynch Syndrome-associated mutation carriers showed a strong correlation to the control group, and two sisters carrying Lynch Syndrome-associated mutations, with no significant difference in lifestyle and similar chronological age, were assigned very different DNAm age. CONCLUSIONS: Future studies will be required to explore, in larger patient populations, whether specific epigenetic age acceleration is predictive of time-to-cancer development, treatment response, and survival. Epigenetic clock DNAm metrics may be affected by the presence of cancer mutations in the germline, and thus show promise of potential clinical utility for stratified surveillance strategies based on the relative risk for imminent emergence of tumor lesions in otherwise healthy Lynch Syndrome-associated mutation carriers.

Endoscopic endonasal resection of clival xanthoma: case report and literature review.

Bone xanthoma is an extremely rare and benign tumor in terms of its nature and growth over time. We describe the first case coexisting with ventriculomegaly secondary to aqueduct stenosis (non-tumoral hydrocephalus), the second xanthoma of the clivus described to date. The patient was a 51-year-old woman with headaches and absence seizures. Axial T1-weighted MRI showed a well-demarcated, hypointense, osteolytic, 25 × 18 × 15 mm lesion with cortical erosion located at the right margin of the clivus. Sagittal T2-weighted MRI demonstrated a hypointense mass without associated edema. Sagittal gadolinium-enhanced T1-weighted MRI showed contrast uptake with a partially hypointense rim. The increased ventricular size without periventricular edema was associated with aqueduct stenosis, and there was no contiguity with the tumor. A neuronavigation image-guided transsphenoidal approach was chosen to perform a macroscopically complete resection. Intraoperative histopathological study showed a chordoma of the clivus. Exhaustive postsurgical study revealed the benign nature of a bone xanthoma. Given the finding of a clival lesion, the differential diagnosis is essentially with other malignant entities with a rapidly fatal outcome, such as metastases, or with a possible invasive evolution, such as clivus chordomas. This report describes the clinical, radiological, and pathological keys for such differentiation in order to avoid unnecessarily aggressive treatment with ablative surgery and radiotherapy.

Valor de la resonancia magnética en la medición del espesor tumoral en el cáncer de lengua: correlación del espesor radiológico con el espesor anatomopatológico en una muestra de 15 pacientes / Magnetic resonance imaging for measuring tumour thickness in cancer of the tongue: Correlation with the histopathological thickness in a sample of 15 patients

Objetivo: El propósito de este estudio ha sido estudiar la correlación de la medida del espesor radiológico en el cáncer de lengua en el estudio prequirúrgico por resonancia magnética respecto al espesor anatomopatológico tras la resección tumoral. El espesor tumoral es un factor predictivo para la presencia de metástasis cervicales, además de ser un factor pronóstico independiente para la supervivencia global y libre de enfermedad. La medida del espesor en estadios precoces es crucial para determinar la actitud terapéutica en estos pacientes. Material y método: Análisis retrospectivo de 15 pacientes intervenidos en el Servicio de Cirugía Maxilofacial del Hospital Regional Universitario Carlos Haya en el periodo 2008-2010. Se realizaron mediciones del espesor radiológico por resonancia magnética en secuencias T1 con contraste y se estudió la correlación respecto al espesor anatomopatológico de la pieza quirúrgica. Resultados: Al realizar el test de correlación lineal de Pearson con ambas medidas hallamos un índice de correlación del 0,897, lo cual apunta hacia una correlación positiva y fuerte. Conclusiones: La resonancia magnética es útil en la evaluación prequirúrgica en el cáncer de lengua y ha demostrado ser una prueba diagnóstica fiable en la medición del espesor tumoral (AU)

Objective: The aim of this study was to analyse the correlation between the radiological thickness of cancer of the tongue in the pre-surgical study using magnetic resonance imaging and the histopathological thickness after the tumour resection. The tumour thickness is a predictive factor for the presence of neck metastases, as well as an independent prognostic factor of overall and disease free survival. The measuring of the thickness in the early stages is essential to determine the therapeutic response in these patients. Material and method: A retrospective analysis was performed on 15 patients subjected to surgery in the Maxillofacial Surgery Department HRU Carlos Haya in the period 2008-2010. Measurements of the radiological thickness were made using magnetic resonance in T1sequences with contrast, and the correlation with histopathological thickness of the surgical piece was analysed. Results: Using the Pearson linear correlation test with both measurements, there was a correlation of 0.897, which indicated a positive and strong agreement. Conclusions: Magnetic resonance is useful in the pre-surgical evaluation in cancer of the tongue and has shown to be a reliable diagnostic test for measuring tumour thickness (AU)

Malaria inhibits surface expression of complement receptor 1 in monocytes/macrophages, causing decreased immune complex internalization.

Complement receptor 1 (CR1) expressed on the surface of phagocytic cells binds complement-bound immune complexes (IC), playing an important role in the clearance of circulating IC. This receptor is critical to prevent accumulation of IC, which can contribute to inflammatory pathology. Accumulation of circulating IC is frequently observed during malaria, although the factors contributing to this accumulation are not clearly understood. We have observed that the surface expression of CR1 on monocytes/macrophages and B cells is strongly reduced in mice infected with Plasmodium yoelii, a rodent malaria model. Monocytes/macrophages from these infected mice present a specific inhibition of complement-mediated internalization of IC caused by the decreased CR1 expression. Accordingly, mice show accumulation of circulating IC and deposition of IC in the kidneys that inversely correlate with the decrease in CR1 surface expression. Our results indicate that malaria induces a significant decrease on surface CR1 expression in the monocyte/macrophage population that results in deficient internalization of IC by monocytes/macrophages. To determine whether this phenomenon is found in human malaria patients, we have analyzed 92 patients infected with either P. falciparum (22 patients) or P. vivax (70 patients) , the most prevalent human malaria parasites. The levels of surface CR1 on peripheral monocytes/macrophages and B cells of these patients show a significant decrease compared with uninfected control individuals in the same area. We propose that this decrease in CR1 plays an essential role in impaired IC clearance during malaria.