Differential presence of exons (DPE): sequencing liquid biopsy by NGS. A new method for clustering colorectal Cancer patients.

Differential presence of exons (DPE) by next generation sequencing (NGS) is a method of interpretation of whole exome sequencing. This method has been proposed to design a predictive and diagnostic algorithm with clinical value in plasma from patients bearing colorectal cancer (CRC). The aim of the present study was to determine a common exonic signature to discriminate between different clinical pictures, such as non-metastatic, metastatic and non-disease (healthy), using a sustainable and novel technology in liquid biopsy.Through DPE analysis, we determined the differences in DNA exon levels circulating in plasma between patients bearing CRC vs. healthy, patients bearing CRC metastasis vs. non-metastatic and patients bearing CRC metastasis vs. healthy comparisons. We identified a set of 510 exons (469 up and 41 down) whose differential presence in plasma allowed us to group and classify between the three cohorts. Random forest classification (machine learning) was performed and an estimated out-of-bag (OOB) error rate of 35.9% was obtained and the predictive model had an accuracy of 75% with a confidence interval (CI) of 56.6-88.5.In conclusion, the DPE analysis allowed us to discriminate between different patho-physiological status such as metastatic, non-metastatic and healthy donors. In addition, this analysis allowed us to obtain very significant values with respect to previous published results, since we increased the number of samples in our study. These results suggest that circulating DNA in patient's plasma may be actively released by cells and may be involved in intercellular communication and, therefore, may play a pivotal role in malignant transformation (genometastasis).

Frecuencia de la mutación 35delG en pacientes con hipoacusia prelingual no sindrómica de herencia autosómica recesiva / Frequency of 35del G mutation among patients affected by a recessive non syndromic autosomic prelingual deafness

Se exploró la presencia de la mutación 35delG por el método dereacción en cadena de la polimerasa descrito por Store, en 32 pacientes,familiarmente no relacionados, con pérdida auditiva prelingual nosindrómica de posible herencia autosómica recesiva. Este cambiogenético fue hallado en 13 de los casos estudiados, 7 en homocigosisy 6 en heterocigosis. La pérdida auditiva es la alteración sensorialmás común en humanos. Se estimó que más de la mitad de los casosera de origen genético, y la forma más frecuente resultó la sorderaprelingual autosómica recesiva asociada a la mutación 35delG. Losresultados indicaron que esta mutación se pudiera hallar en una granproporción en el medio cubano y apoyaron la hipótesis, sustentadapor hallazgos clínicos, de que la sordera hereditaria es un paradigmade la heterogeneidad genética…(AU)