Nuestro nuevo artículo en Nature

Nuestro nuevo artículo de Genómica del Cáncer Cérvicouterino acaba de ser publicado

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12881.html

Básicamente logramos encontrar varias nuevas mutaciones. Tres o cuatro de ellas muy interesantes, como HLA, MAPK1 y (para nosotros) CBFB yERBB2. La primera es importante dado a que podría ser el primer ejemplo de drivers inmunológicos, la segunda dado a que es una cinasa (potencialmente “drogable”) y la tercera se comparte con cáncer de mama. Asimismo hay alguna evidencia inicial de que la inserción del HPV puede ser también importante en la patogénesis, dado a que se inserta en algunos genes importantes.  A partir de aquí nos falta todavía validar los genes más importantes en un número grande de pacientes, realizar algo similar con RNA y con esto, considerar la validez de usar algunos de los genes para diagnóstico/pronóstico y terapia.

http://eleconomista.com.mx/entretenimiento/2014/01/27/hallan-nuevos-genes-cancer-cervicouterino

http://www.jornada.unam.mx/ultimas/2014/01/28/hallan-dos-mutaciones-geneticas-relacionadas-con-el-cancer-1512.html

Landscape of genomic alterations in cervical carcinomas.

Ojesina AI1, et al. Nature. 2013 Dec 25. doi: 10.1038/nature12881

Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established. Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as several copy-number alterations in the pathogenesis of cervical carcinomas. Here we report whole-exome sequencing analysis of 115 cervical carcinoma-normal paired samples, transcriptome sequencing of 79 cases and whole-genome sequencing of 14 tumour-normal pairs. Previously unknown somatic mutations in 79 primary squamous cell carcinomas include recurrent E322K substitutions in the MAPK1 gene (8%), inactivating mutations in the HLA-B gene (9%), and mutations in EP300 (16%), FBXW7 (15%), NFE2L2 (4%), TP53 (5%) and ERBB2 (6%). We also observe somatic ELF3 (13%) and CBFB (8%) mutations in 24 adenocarcinomas. Squamous cell carcinomas have higher frequencies of somatic nucleotide substitutions occurring at cytosines preceded by thymines (Tp*C sites) than adenocarcinomas. Gene expression levels at HPV integration sites were statistically significantly higher in tumours with HPV integration compared with expression of the same genes in tumours without viral integration at the same site. These data demonstrate several recurrent genomic alterations in cervical carcinomas that suggest new strategies to combat this disease.

Regulación dinámica de DNA extracromosomal

Interesante artículo. ¿Cual será el mecanismo para producir estos fragmentos extracromosomales? La creación  de cromosomas doble minuta y selección? Sin embargo habría que explicar como a partir de una célula se puede reproducir la población (debería ser un mecanismo rápido y lo suficientemente importante para seleccionarse).

Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA Science 3 January 2014: Vol. 343 no. 6166 pp. 72-76

Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring distinct cellular phenotypes to reach an optimal equilibrium for growth. Resistance to EGFR TKIs is shown to occur by elimination of mutant EGFR from extrachromosomal DNA. After drug withdrawal, reemergence of clonal EGFR mutations on extrachromosomal DNA follows. These results indicate a highly specific, dynamic, and adaptive route by which cancers can evade therapies that target oncogenes maintained on extrachromosomal DNA.

 

PhD survival guide

Some brief advice for PhD students
Leonardo Almeida-Souza & Jonathan Baets
By now you have secured your place on a PhD programme, your project is beginning to crystallize and you have a paid position or a fellowship to support you financially during your time in the lab. Time to put your brain and body to work at last. But beware, although your PhD will have many thrilling moments of discovery and insight, there will also be many pitfalls and perils to overcome or avoid. Here, we hope to summarize some of those challenges and offer a few tips that might help budding PhD students survive the bad times and enjoy the good
link (dentro del INMEGEN)

INTERNATIONAL CANCER GENOME CONSORTIUM

Este es el proyecto global en el que participa el INMEGEN. El ICGC es uno de los dos proyectos más grandes a nivel mundial (el oro es el TCGA). México es el único país latinoamericano en participar. En él están 13 países y 390 grupos de investigación.

ICGC Goal: To obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in 50 different tumor types and/or subtypes which are of clinical and societal importance across the globe.

!Al final esperamos tener 18000 tumores secuenciados!

NewImage

 

Pueden echarle un vistazo en icgc.org

 

Ciencia en México (y el mundo)

Aunque el mapa de como estamos en producción científica es poco halagador, lo interesante es que hemos crecido, sobre todo comparando a otros países (incluído EU). Compare la primera foto con la segunda. Este tipo de gráficas se parecen al homúnculo de Penfield (http://es.wikipedia.org/wiki/Homúnculo) 🙂

 

PRODUCCION CIENTIFICA

205

CRECIMIENTO PRODUCCION CIENTIFICA

206

 

 

fuente http://www.worldmapper.org

Notable advance for 2011 (from Nature Medicine)

Cancer biology: BET-ting on chromatin

Tumor development often involves genomic changes that affect protein expression, so chromatin alterations have received a lot of attention as possible therapeutic targets. A handful of recent studies support this idea by identifying a role for the bromodomain and extraterminal (BET) family of transcriptional regulators, which bind and recognize histone acetylation, in several human hematological malignancies.

Four independent groups—from Boston’s Dana-Farber Cancer Institute, New York state’s Cold Spring Harbor Laboratory, the UK’s Cambridge University and Massachusetts’s Constellation Pharmaceuticals—started from different points and used different models, but they all converged on the finding that interfering with the function of BET proteins reduces the transcription of key oncogenes such as Myc, arrests cell-cycle progression and leads to apoptosis (Cell 146, 904–917, 2011; Nature 478, 524–528 & 529–533, 2011; Proc. Natl. Acad. Sci. USA 108, 16669–16674, 2011).

Crucially, the four studies highlighted the clinical implications of this finding by showing that small-molecule inhibitors of BET family members had therapeutic effects in mouse models of leukemia, lymphoma and myeloma, as well as in primary cells isolated from people with cancer. —JCL

International network of cancer genome projects

Nature 464, 993-998 (15 April 2010) doi:10.1038/nature08987

International Cancer Genome Consortium

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Salud en Mexico. PLOS Medicine

Characterizing the Epidemiological Transition in Mexico: National and Subnational Burden of Diseases, Injuries, and Risk Factors

Gretchen Stevens1,2,3*, Rodrigo H. Dias2, Kevin J. A. Thomas4, Juan A. Rivera5, Natalie Carvalho2, Simón Barquera5, Kenneth Hill2, Majid Ezzati1,2

1 Harvard School of Public Health, Boston, Massachusetts, United States of America, 2 Harvard Initiative for Global Health, Cambridge, Massachusetts, United States of America, 3 World Health Organization, Geneva, Switzerland, 4 Pennsylvania State University, University Park, Pennsylvania, United States of America, 5 Instituto Nacional de Salud Pública, Cuernavaca, Mexico

Background

Rates of diseases and injuries and the effects of their risk factors can have substantial subnational heterogeneity, especially in middle-income countries like Mexico. Subnational analysis of the burden of diseases, injuries, and risk factors can improve characterization of the epidemiological transition and identify policy priorities.

Methods and Findings

We estimated deaths and loss of healthy life years (measured in disability-adjusted life years [DALYs]) in 2004 from a comprehensive list of diseases and injuries, and 16 major risk factors, by sex and age for Mexico and its states. Data sources included the vital statistics, national censuses, health examination surveys, and published epidemiological studies. Mortality statistics were adjusted for underreporting, misreporting of age at death, and for misclassification and incomparability of cause-of-death assignment. Nationally, noncommunicable diseases caused 75% of total deaths and 68% of total DALYs, with another 14% of deaths and 18% of DALYs caused by undernutrition and communicable, maternal, and perinatal diseases. The leading causes of death were ischemic heart disease, diabetes mellitus, cerebrovascular disease, liver cirrhosis, and road traffic injuries. High body mass index, high blood glucose, and alcohol use were the leading risk factors for disease burden, causing 5.1%, 5.0%, and 7.3% of total burden of disease, respectively. Mexico City had the lowest mortality rates (4.2 per 1,000) and the Southern region the highest (5.0 per 1,000); under-five mortality in the Southern region was nearly twice that of Mexico City. In the Southern region undernutrition and communicable, maternal, and perinatal diseases caused 23% of DALYs; in Chiapas, they caused 29% of DALYs. At the same time, the absolute rates of noncommunicable disease and injury burdens were highest in the Southern region (105 DALYs per 1,000 population versus 97 nationally for noncommunicable diseases; 22 versus 19 for injuries).

Conclusions

Mexico is at an advanced stage in the epidemiologic transition, with the majority of the disease and injury burden from noncommunicable diseases. A unique characteristic of the epidemiological transition in Mexico is that overweight and obesity, high blood glucose, and alcohol use are responsible for larger burden of disease than other noncommunicable disease risks such as tobacco smoking. The Southern region is least advanced in the epidemiological transition and suffers from the largest burden of ill health in all disease and injury groups.