SDHB exon 1 deletion: A recurrent germline mutation in Colombian patients with pheochromocytomas and paragangliomas.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) (known as PPGL in combination) are rare neuroendocrine tumors of the adrenal medulla and extra-adrenal ganglia. About 40% of the patients with PPGL have a hereditary predisposition. Here we present a case-series of 19 unrelated Colombian patients with a clinical diagnosis of PPGL tumors that underwent germline genetic testing as part of the Hereditary Cancer Program developed at the Instituto Nacional de Cancerología, Colombia (INC-C), the largest reference cancer center in the country. Ten of 19 patients (52.63%) were identified as carriers of a pathogenic/likely pathogenic (P/LP) germline variant in a known susceptibility gene. The majority of the P/LP variants were in the SDHB gene (9/10): one corresponded to a nonsense variant c.268C>T (p.Arg90*) and eight cases were found to be carriers of a recurrent CNV consisting of a large deletion of one copy of exon 1, explaining 42% (8/19) of all the affected cases. Only one additional case was found to be a carrier of a missense mutation in the VHL gene: c.355T>C (p.Phe119Leu). Our study highlights the major role of SDHB in Colombian patients with a clinical diagnosis of PGL/PCC tumors and supports the recommendation of including the analysis of large deletions/duplications of the SDHB gene as part of the genetic counselling to improve the detection rate of hereditary cases and their clinical care.

Evaluación de la metilación del DNA en tejidos de cáncer colorrectal fijados en formalina y embebidos en parafina (FFPE) / Evaluation of DNA methylation in formalin-fixed, paraffin embedded colorectal cancer tissues (FFPE)

Resumen Las alteraciones en la metilación de dinucleótidos CpG en regiones promotoras es uno de los mecanismos epigenéticos implicados en cáncer que tiene uso potencial como biomarcador. Su evaluación, a partir de tejidos fijados en formalina y embebidos en parafina (FFPE), representa un gran desafío dadas la degradación parcial, el entrecruzamiento y las bajas cantidades del DNA obtenido. En esta nota técnica, describimos un protocolo para el estudio del estado de metilación del promotor distal del proto-oncogén K-RAS, a partir de varias muestras obtenidas de dos tejidos FFPE de cáncer colorrectal con antigüedad de 11 años. Se empleó un protocolo de conversión con bisulfito alternativo al usual; se usó una DNA polimerasa modificada y una PCR anidada y se optimizó la secuenciación directa del DNA convertido con bisulfito. Este protocolo podría ser aplicado para determinar estados de metilación en otros genes y tipos de cáncer en tejidos FFPE.

Abstract Alterations in the methylation of CpG dinucleotides in promoter regions is one of the epigenetic mechanisms involved in cancer that has potential use as a biomarker. Its evaluation from formalin-fixed and paraffin-embedded (FFPE) tissues represents a great challenge given the partial degradation, crosslinking, and low amounts of the obtained DNA. In this technical note we describe a protocol for the study of the methylation status of the distal promoter of the K-RAS proto-oncogene from several samples obtained from two 11-years old FFPE tissues of colorectal cancer. An alternative bisulfite conversion protocol to the usual one was used; a modified DNA polymerase and a nested PCR were used and the direct sequencing of the converted DNA with bisulfite was optimized. This protocol could be applied to determine methylation states in other genes and types of cancer.

Randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults.

A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 x 10(9)CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.

Mutación del gen de la menina: desde el hiperparatiroidismo familiar aislado a la neoplasia endocrina múltiple de tipo 1: [revisión] / Mutation of the menin gen: from isolated familial hyperparathyroidism to the multiple endocrine neoplasia syndrome type 1: [review]

La menina es una proteína supresora de tumor codificada por el gen MEN1, cuya mutación produce procesos neoplásicos en múltiples tejidos del organismo que pueden manifestarse por generaciones como síndromes familiares. La mutación genera un espectro de enfermedad que va desde el hiperparatiroidismo familiar aislado hasta la neoplasia endocrina múltiple de tipo 1, caracterizada por neoplasias de paratiroides, hipófisis anterior, páncreas endocrino y duodeno, entre otras. Como ejemplo, se presentan dos casos de pacientes con neoplasias endocrinas secundarias a la mutación del gen MEN1. Se revisa la información actual sobre la etiopatogenia y carcinogénesis entendidos apenas recientemente, al igual que otras mutaciones involucradas en los síndromes neoplásicos expuestos y se dan unas recomendaciones finales.

Menin is a tumor suppressor protein, encoded by the MEN1 gene, whose mutation can generate neoplastic disease in multiple tissues of the human body, which for generations can manifest as familial syndromes. The mutation generates a spectrum of diseases ranging from familial isolated hyperparathyroidism to multiple endocrine neoplasia type 1, characterized by neoplasm of parathyroid glands, anterior pituitary, endocrine pancreas and duodenum, among others. We present two cases of patients with endocrine neoplastic disease secondary to menin’s mutation. We review current information regarding its ethiopathogeny and its mechanism of carcinogenesis just recently understood. Additionally we review other mutations involved in the neoplastic syndromes exposed and present some final recommendations.

SIDA: impacto psicosocial

Se realiza un análisis filosófico de un dilema bioético importante en nuestro medio: la ética médica y el Sindrome de Inmunodeficiencia Adquirida (SIDA), el humanismo como base de la relación médico-paciente y la reflexión acerca del impacto psicosocial y económico del SIDA, y cómo perjudica en mayor medida a la mujer y a la niñez(AU)