64 research outputs found
Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer
Background
Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma.
Methodology/Principal Findings
Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genesβWHSC1L1, LETM2, and FGFR1βis amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition.
Conclusions/Significance
These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.Novartis Pharmaceuticals CorporationAmerican Lung AssociationUniting Against Lung CancerSara Thomas Monopoli FundSeaman FoundationIndia. Dept. of BiotechnologyNational Lung Cancer Partnershi
Signatures of mutational processes in human cancer.
All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy
The relationship between the cell length, adhesion to acrylic and relative cell surface hydrophobicity of Candida parapsilosis
Candida parapsilosis is an emerging opportunistic pathogen which causes systemic and superficial infections in immunocompromised hosts. Successful colonization and subsequent infection of the host by a microorganism depends upon its ability to adhere to host surfaces, and its relative cell surface hydrophobicity (CSH) is a contributory physical force involved in the process. During a comprehensive study of a battery of C. parapsilosis isolates, we noted wide variations in their cell size. Hence we examined the relationship between the cell length, in vitro adhesion to acrylic surfaces and relative CSH of 24 isolates of C. parapsilosis from superficial and systemic sources. A strong positive correlation was observed between the cell length and adhesion of Candida to acrylic surfaces (r = 0.56; P = 0.004) as well as the cell length and the relative CSH, as measured by a hydrocarbon assay method (r = 0.72, P = 0.0001). Further, the cell length of both the superficial and systemic isolates correlated well with their CSH (r = 0.63, P = 0.01; r = 0.63, P = 0.03 for superficial and systemic isolates, respectively). These data provide a tantalizing glimpse of the structural and functional dynamics of the candidal cell surface.link_to_subscribed_fulltex
Unilateral papilledema in a 21-year-old diabetic patient β consequence of an improved blood glucose control?
Cellβcell adhesion genes CTNNA2 and CTNNA3 are tumour suppressors frequently mutated in laryngeal carcinomas
Open Access to Large Scale Datasets Is Needed to Translate Knowledge of Cancer Heterogeneity into Better Patient Outcomes
Primary Chemotherapy and Radiation as a Treatment Strategy for HPV-Positive Oropharyngeal Cancer
The incidence of human papillomavirus-positive oropharyngeal cancer (HPV/OPSCC) is rapidly increasing, which will represent a major public health burden for decades to come. Although HPV/OPSCC is generally associated with a better prognosis than HPV-negative OPSCC, the survival rate of individuals with higher-risk clinical and pathologic features remains unchanged. Emerging evidence suggests that HPV/OPSCC is pathologically and molecularly distinct from HPV-negative OPSCC. This review focuses on summarizing treatment strategies for HPV/OPSCC by reviewing the peer-reviewed literature and noting ongoing and planned clinical trials in this disease. We also discuss the potential of designing targeted therapy based on the recent genomic findings of HPV/OPSCC
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Detection of somatic point substitutions is a key step in characterizing the cancer genome. However, existing methods typically miss low-allelic-fraction mutations that occur in only a subset of the sequenced cells owing to either tumor heterogeneity or contamination by normal cells. Here we present MuTect, a method that applies a Bayesian classifier to detect somatic mutations with very low allele fractions, requiring only a few supporting reads, followed by carefully tuned filters that ensure high specificity. We also describe benchmarking approaches that use real, rather than simulated, sequencing data to evaluate the sensitivity and specificity as a function of sequencing depth, base quality and allelic fraction. Compared with other methods, MuTect has higher sensitivity with similar specificity, especially for mutations with allelic fractions as low as 0.1 and below, making MuTect particularly useful for studying cancer subclones and their evolution in standard exome and genome sequencing data.National Institutes of Health (U.S.) (Grant U54HG003067)National Institutes of Health (U.S.) (Grant U24CA143845
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