Author
Ignacio G. Bravo
Other affiliations: University of León, German Cancer Research Center, University of Münster ...read more
Bio: Ignacio G. Bravo is an academic researcher from Centre national de la recherche scientifique. The author has contributed to research in topics: Gene & Codon usage bias. The author has an hindex of 35, co-authored 124 publications receiving 6161 citations. Previous affiliations of Ignacio G. Bravo include University of León & German Cancer Research Center.
Topics: Gene, Codon usage bias, Genome, Phylogenetic tree, Papillomaviridae
Papers published on a yearly basis
Papers
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TL;DR: The high-risk HPV types are a cause of several important human cancers, including almost all cases of cervical cancer, a large proportion of other anogenital cancers and a growing number of head and neck tumours.
1,108 citations
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German Cancer Research Center1, University of Barcelona2, National University of Colombia3, Manchester Royal Infirmary4, Charles University in Prague5, University of Ljubljana6, Universidad Nacional de Asunción7, University of Birmingham8, Université de Montréal9, Pompeu Fabra University10, Mexican Social Security Institute11, Catholic University of Korea12, University of Lagos13, Bangabandhu Sheikh Mujib Medical University14, Hospital General de México15, NewYork–Presbyterian Hospital16, Gomel State Medical University17, Instituto Português de Oncologia Francisco Gentil18, University of the Philippines19, Koç University20, Hacettepe University21, Indian Council of Medical Research22, University of Hawaii23, Cedars-Sinai Medical Center24, Hospital General San Juan de Dios25, Universidad Nacional Autónoma de Honduras26, Bayero University Kano27, Central University of Venezuela28, University of Chile29, Instituto Potosino de Investigación Científica y Tecnológica30
TL;DR: This large international study to estimate fractions of head and neck cancers attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation confirms the important role ofHPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.
Abstract: BACKGROUND:
We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation.
METHODS:
Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results.
RESULTS:
A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America.
CONCLUSIONS:
HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.
548 citations
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TL;DR: Multiplex human papillomavirus genotyping (MPG), a quantitative and sensitive high-throughput procedure for the identification of multiple high- and low-risk genital HPV genotypes in a single reaction appears to be highly suitable for large-scale epidemiological studies and vaccination trials as well as for routine diagnostic purposes.
Abstract: Typing of human papillomaviruses (HPV) by DNA hybridization procedures, such as reverse line blot (RLB) assay, is sensitive and well validated. However, the application of these assays to high-throughput analyses is limited. Here, we describe the development of multiplex human papillomavirus genotyping (MPG), a quantitative and sensitive high-throughput procedure for the identification of multiple high- and low-risk genital HPV genotypes in a single reaction. MPG is based on the amplification of HPV DNA by a general primer PCR (GP5+/6+) and the subsequent detection of the products with type-specific oligonucleotide probes coupled to fluorescence-labeled polystyrene beads (Luminex suspension array technology). Up to 100 different HPV types can be detected simultaneously with MPG, and the method is fast and labor saving. We detected all 22 HPV types examined with high specificity and reproducibility (the median interplate coefficient of variation was below 10%). Detection limits for the different HPV types varied between 100 and 800 pg of PCR products. We compared the performance of MPG to an established RLB assay on GP5+/6+-PCR products derived from 94 clinical samples. The evaluation showed an excellent agreement (kappa = 0.922) but also indicated a higher sensitivity of MPG. In conclusion, MPG appears to be highly suitable for large-scale epidemiological studies and vaccination trials as well as for routine diagnostic purposes.
510 citations
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TL;DR: The CAIcal server provides a complete set of tools to assess codon usage adaptation and to help in genome annotation, including the automated calculation of CAI and its expected value.
Abstract: The Codon Adaptation Index (CAI) was first developed to measure the synonymous codon usage bias for a DNA or RNA sequence. The CAI quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set. We describe here CAIcal, a web-server available at http://genomes.urv.es/CAIcal
that includes a complete set of utilities related with the CAI. The server provides useful important features, such as the calculation and graphical representation of the CAI along either an individual sequence or a protein multiple sequence alignment translated to DNA. The automated calculation of CAI and its expected value is also included as one of the CAIcal tools. The software is also free to be downloaded as a standalone application for local use. The CAIcal server provides a complete set of tools to assess codon usage adaptation and to help in genome annotation. This article was reviewed by Purificacion Lopez-Garcia, Dan Graur, Rob Knight and Shamil Sunyaev.
410 citations
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University of Alabama1, International Agency for Research on Cancer2, University of California, San Francisco3, Ohio State University4, Medical Research Council5, University of Manchester6, University of Cambridge7, University of Antwerp8, University of Ljubljana9, Queen Mary University of London10, National Institutes of Health11, Centers for Disease Control and Prevention12, University of Western Ontario13, University of New South Wales14, University of Cape Town15, McGill University16, VU University Amsterdam17, Harvard University18
TL;DR: There must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries.
352 citations
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University of Pittsburgh1, University of Texas MD Anderson Cancer Center2, Stanford University3, University of Duisburg-Essen4, University of Chicago5, Institut Gustave Roussy6, University of Michigan7, Emory University8, Complutense University of Madrid9, Harvard University10, University of Zurich11, Kobe University12, Bristol-Myers Squibb13, Ohio State University14
TL;DR: Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy.
Abstract: BackgroundPatients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti–programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. MethodsIn this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. ResultsThe median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to...
3,246 citations
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TL;DR: In this paper, the coding exons of the family of 518 protein kinases were sequenced in 210 cancers of diverse histological types to explore the nature of the information that will be derived from cancer genome sequencing.
Abstract: AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore
PL02-05
All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.
2,737 citations
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TL;DR: It is discussed that based on emerging species concepts derived from genome sequences, PV types could be promoted to the taxonomic level of species, but it is not recommended to implement this change at the current time.
1,496 citations
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TL;DR: Evidence is now accumulating that alternative splicing coordinates physiologically meaningful changes in protein isoform expression and is a key mechanism to generate the complex proteome of multicellular organisms.
1,367 citations