RESUMEN
L1 retrotransposons comprise 17% of the human genome and are its only autonomous mobile elements. Although L1-induced insertional mutagenesis causes Mendelian disease, their mutagenic load in cancer has been elusive. Using L1-targeted resequencing of 16 colorectal tumor and matched normal DNAs, we found that certain cancers were excessively mutagenized by human-specific L1s, while no verifiable insertions were present in normal tissues. We confirmed de novo L1 insertions in malignancy by both validating and sequencing 69/107 tumor-specific insertions and retrieving both 5' and 3' junctions for 35. In contrast to germline polymorphic L1s, all insertions were severely 5' truncated. Validated insertion numbers varied from up to 17 in some tumors to none in three others, and correlated with the age of the patients. Numerous genes with a role in tumorigenesis were targeted, including ODZ3, ROBO2, PTPRM, PCM1, and CDH11. Thus, somatic retrotransposition may play an etiologic role in colorectal cancer.
Asunto(s)
Neoplasias Colorrectales/genética , Elementos de Nucleótido Esparcido Largo/genética , Retroelementos/genética , Genoma Humano , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Metilación , Inestabilidad de Microsatélites , Mutagénesis Insercional , Fenotipo , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: Surgical boot camps enhance the confidence of medical students and surgical interns. The impact of boot camps on the confidence of post-graduate year (PGY) 2 residents is unknown. We hypothesized that a postinternship boot camp would improve the confidence of PGY-2 residents in managing their newfound responsibilities. We also hypothesized that the effect of a tailored high-impact boot camp would persist over time. DESIGN: A 2-hour boot camp at our simulation center was implemented for PGY-2 residents in 2016 and 2017. Confidence in handling boot camp scenarios was measured on a 1 to 5 Likert scale before and after the boot camp. Three-month follow-up was assessed in the 2017 cohort. PARTICIPANTS: Thirty-one PGY-2 residents (nâ¯=â¯16 in 2016, nâ¯=â¯15 in 2017) completed the boot camp. RESULTS: Residents reported increased confidence in placing central lines (p < 0.001), placing chest tubes (pâ¯=â¯0.01), managing emergency airways (p < 0.001), running a code (pâ¯=â¯0.03), and fulfilling the role of in-house senior resident (p < 0.001). Three-month follow-up in 2017 (nâ¯=â¯10) demonstrated no difference in confidence compared to postboot camp results. CONCLUSIONS: Boot camps can durably improve confidence in skills expected of PGY-2 residents assuming in-house senior resident responsibilities.