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1.
Genome Res ; 24(10): 1559-71, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25186909

RESUMEN

Chromosomal structural variations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural variations, we analyzed eight breast tumor samples with a focus on regions of gene amplification using mate-pair sequencing of long-insert genomic DNA with matched transcriptome profiling. We found that tandem duplications appear to be early events in tumor evolution, especially in the genesis of amplicons. In a detailed reconstruction of events on chromosome 17, we found large unpaired inversions and deletions connect a tandemly duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor suppressor locus. This series of events appeared to be unusually common when examined in larger genomic data sets of breast cancers albeit using approaches with lesser resolution. Using siRNAs in breast cancer cell lines, we showed that the 17q21.3 amplicon harbored a significant number of weak oncogenes that appeared consistently coamplified in primary tumors. Down-regulation of BRCA1 expression augmented the cell proliferation in ERBB2-transfected human normal mammary epithelial cells. Coamplification of other functionally tested oncogenic elements in other breast tumors examined, such as RIPK2 and MYC on chromosome 8, also parallel these findings. Our analyses suggest that structural variations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously and that such oncogenic cassettes are favored during the evolution of a cancer.


Asunto(s)
Proteína BRCA1/genética , Neoplasias de la Mama/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 17/genética , Receptor ErbB-2/genética , Secuencia de Bases , Línea Celular Tumoral , Femenino , Amplificación de Genes , Duplicación de Gen , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Datos de Secuencia Molecular , Análisis de Secuencia de ADN
2.
Am J Infect Control ; 49(12): 1469-1473, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34551335

RESUMEN

BACKGROUND: Healthcare workers are at increased risk of SARS-CoV-2 infection. The positivity rates in hospitals that do not receive patients with COVID-19, such as the National Cancer Institute (INCan) in Mexico, and the associated factors are unknown. OBJECTIVE: To assess the incidence and factors associated with SARS-CoV-2 infection in health workers at INCan. METHODS: A cohort study of 531 workers who were followed for 6 months. RT-PCR analysis of saliva and nasopharyngeal swab samples were used in the baseline and to confirm cases during follow-up The incidence rate ratio was calculated according to the measured characteristics and the associated factors were calculated using logistic regression models. RESULTS: Out of 531 workers, 9.6% tested positive for SARS-CoV-2, Being male (RR: 2.07, 95% CI: 1.1-3.8, P = .02), performing administrative tasks (RR: 1.99, 95% CI: 1.0-3.9, P = .04), and having relatives also working at INCan (RR: 3.7, 95% CI: 1.4-9.5, P < .01) were associated with higher positivity rates. DISCUSSION: Incidence of positive cases in health workers were similar to that reported in non-COVID hospitals from other countries. CONCLUSIONS: Even though active surveillance helped to detect a significant number of asymptomatic infections, it is still necessary to reinforce preventive measures in non-medical staff to prevent nosocomial transmission.


Asunto(s)
COVID-19 , Neoplasias , Estudios de Cohortes , Personal de Salud , Hospitales , Humanos , Masculino , México/epidemiología , Neoplasias/epidemiología , Derivación y Consulta , SARS-CoV-2
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