scholarly journals Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations

2017 ◽  
Author(s):  
David Tamborero ◽  
Carlota Rubio-Perez ◽  
Jordi Deu-Pons ◽  
Michael P Schroeder ◽  
Ana Vivancos ◽  
...  
Keyword(s):  
Open Access ◽  
Genome Sequencing ◽  
Clinical Relevance ◽  
Cancer Genome ◽  
Cancer Therapies ◽  
Cancer Genes ◽  
Genomic Alterations ◽  
Anti Cancer ◽  
Uncertain Significance ◽  
Tumor Genome

AbstractWhile tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Most of the alterations observed in tumors, including those in well-known cancer genes, are of uncertain significance. Moreover, the information on tumor genomic alterations shaping the response to existing therapies is fragmented across the literature and several specialized resources. Here we present the Cancer Genome Interpreter (http://www.cancergenomeinterpreter.org), an open access tool that we have implemented to annotate genomic alterations and interpret their possible role in tumorigenesis and in the response to anti-cancer therapies.

A heuristic platform for clinical interpretation of cancer genome sequencing data.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10502-10502
Author(s):  
Eliezer Mendel Van Allen ◽  
Nikhil Wagle ◽  
Gregory Kryukov ◽  
Alexis Ramos ◽  
Gad Getz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genome Sequencing ◽  
Heuristic Algorithm ◽  
Genetic Alterations ◽  
Cancer Genome ◽  
Clinical Samples ◽  
Whole Genome ◽  
Cancer Genes ◽  
Sequencing Data ◽  
Clinical Interpretation

10502 Background: The ability to identify and effectively sort the full spectrum of biologically and therapeutically relevant genetic alterations identified by massively parallel sequencing may improve cancer care. A major challenge involves rapid and rational categorization of data-intensive output, including somatic mutations, insertions/deletions, copy number alterations, and rearrangements into ranked categories for clinician review. Methods: A database of clinically actionable alterations was created, consisting of over 100 annotated genes known to undergo somatic genomic alterations in cancer that may impact clinical decision-making. A heuristic algorithm was developed, which selectively identifies somatic alterations based on the clinically actionable alterations database. Remaining variants are sorted based on additional heuristics, including high priority alterations based on presence in the Cancer Gene Census, biologically significant cancer genes based on presence in COSMIC or MSigDB, and low priority alterations in the same gene family as biologically significant cancer genes. The heuristic algorithm was applied to whole exome sequencing data of clinical samples and whole genome sequencing data from a cohort of prostate cancer samples processed using established Broad Institute pipelines. Results: Application of the heuristic algorithm to the prostate cancer whole genome rearrangement data identified 172 (out of 5978) rearrangements involving actionable genes (averaging 2-3 events per tumor). Furthermore, two clinical samples processed prospectively were analyzed, yielding three potentially actionable alterations for clinical review. Conclusions: The heuristic model for clinical interpretation of next generation sequencing data may facilitate rapid analysis of tumor genomic information for clinician review by identifying and prioritizing alterations that can directly impact care. Our platform can also be applied to research data to prospectively explore clinically relevant findings from existing cohorts. Future analytical approaches using heuristic or probabilistic algorithms should underpin a robust prospective assessment of clinical cancer genome data.

scholarly journals Clinical Tumor Sequencing: Opportunities and Challenges for Precision Cancer Medicine

2015 ◽  
pp. e175-e182 ◽  
Author(s):  
Senthilkumar Damodaran ◽  
Michael F. Berger ◽  
Sameek Roychowdhury
Keyword(s):  
Genome Sequencing ◽  
Clinical Care ◽  
Point Mutations ◽  
Genomic Testing ◽  
Genomic Alterations ◽  
Discovery Research ◽  
Challenges And Opportunities ◽  
Cancer Medicine ◽  
Next Generation Sequencing Ngs ◽  
Tumor Genome

Advances in tumor genome sequencing have enabled discovery of actionable alterations leading to novel therapies. Currently, there are approved targeted therapies across various tumors that can be matched to genomic alterations, such as point mutations, gene amplification, and translocations. Tools to detect these genomic alterations have emerged as a result of decreasing costs and improved throughput enabled by next-generation sequencing (NGS) technologies. NGS has been successfully utilized for developing biomarkers to assess susceptibility, diagnosis, prognosis, and treatment of cancers. However, clinical application presents some potential challenges in terms of tumor specimen acquisition, analysis, privacy, interpretation, and drug development in rare cancer subsets. Although whole-genome sequencing offers the most complete strategy for tumor analysis, its present utility in clinical care is limited. Consequently, targeted gene capture panels are more commonly employed by academic institutions and commercial vendors for clinical grade cancer genomic testing to assess molecular eligibility for matching therapies, whereas whole-exome and transcriptome (RNASeq) sequencing are being utilized for discovery research. This review discusses the strategies, clinical challenges, and opportunities associated with the application of cancer genomic testing for precision cancer medicine.

scholarly journals Whole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiaotong Li ◽  
Sushant Kumar ◽  
Arif Harmanci ◽  
Shantao Li ◽  
Robert R. Kitchen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Cancer Genome ◽  
Whole Genome ◽  
Breast Cancers ◽  
Genomic Alterations ◽  
Genomic Features ◽  
Clonal Architecture

Abstract Background Inflammatory breast cancer (IBC) has a highly invasive and metastatic phenotype. However, little is known about its genetic drivers. To address this, we report the largest cohort of whole-genome sequencing (WGS) of IBC cases. Methods We performed WGS of 20 IBC samples and paired normal blood DNA to identify genomic alterations. For comparison, we used 23 matched non-IBC samples from the Cancer Genome Atlas Program (TCGA). We also validated our findings using WGS data from the International Cancer Genome Consortium (ICGC) and the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We examined a wide selection of genomic features to search for differences between IBC and conventional breast cancer. These include (i) somatic and germline single-nucleotide variants (SNVs), in both coding and non-coding regions; (ii) the mutational signature and the clonal architecture derived from these SNVs; (iii) copy number and structural variants (CNVs and SVs); and (iv) non-human sequence in the tumors (i.e., exogenous sequences of bacterial origin). Results Overall, IBC has similar genomic characteristics to non-IBC, including specific alterations, overall mutational load and signature, and tumor heterogeneity. In particular, we observed similar mutation frequencies between IBC and non-IBC, for each gene and most cancer-related pathways. Moreover, we found no exogenous sequences of infectious agents specific to IBC samples. Even though we could not find any strongly statistically distinguishing genomic features between the two groups, we did find some suggestive differences in IBC: (i) The MAST2 gene was more frequently mutated (20% IBC vs. 0% non-IBC). (ii) The TGF β pathway was more frequently disrupted by germline SNVs (50% vs. 13%). (iii) Different copy number profiles were observed in several genomic regions harboring cancer genes. (iv) Complex SVs were more frequent. (v) The clonal architecture was simpler, suggesting more homogenous tumor-evolutionary lineages. Conclusions Whole-genome sequencing of IBC manifests a similar genomic architecture to non-IBC. We found no unique genomic alterations shared in just IBCs; however, subtle genomic differences were observed including germline alterations in TGFβ pathway genes and somatic mutations in the MAST2 kinase that could represent potential therapeutic targets.

scholarly journals Unique k-mer sequences for validating cancer-related substitution, insertion and deletion mutations

NAR Cancer ◽  
2020 ◽  
Vol 2 (4) ◽  
Author(s):  
HoJoon Lee ◽  
Ahmed Shuaibi ◽  
John M Bell ◽  
Dmitri S Pavlichin ◽  
Hanlee P Ji
Keyword(s):  
Genome Sequencing ◽  
Somatic Mutations ◽  
Variant Calling ◽  
Cancer Genome ◽  
Cancer Genes ◽  
Sequencing Data ◽  
Deletion Mutations ◽  
Insertion And Deletion ◽  
Cancer Genome Sequencing ◽  
Significant Difference

Abstract Cancer genome sequencing has led to important discoveries such as the identification of cancer genes. However, challenges remain in the analysis of cancer genome sequencing. One significant issue is that mutations identified by multiple variant callers are frequently discordant even when using the same genome sequencing data. For insertion and deletion mutations, oftentimes there is no agreement among different callers. Identifying somatic mutations involves read mapping and variant calling, a complicated process that uses many parameters and model tuning. To validate the identification of true mutations, we developed a method using k-mer sequences. First, we characterized the landscape of unique versus non-unique k-mers in the human genome. Second, we developed a software package, KmerVC, to validate the given somatic mutations from sequencing data. Our program validates the occurrence of a mutation based on statistically significant difference in frequency of k-mers with and without a mutation from matched normal and tumor sequences. Third, we tested our method on both simulated and cancer genome sequencing data. Counting k-mer involving mutations effectively validated true positive mutations including insertions and deletions across different individual samples in a reproducible manner. Thus, we demonstrated a straightforward approach for rapidly validating mutations from cancer genome sequencing data.

ANTICANCER EFFECT OF UVARIA GENUS

2014 ◽  
pp. 98-101
Author(s):  
Thi Bich Hien Le ◽  
Viet Duc Ho ◽  
Thi Hoai Nguyen
Keyword(s):  
Biological Activities ◽  
Current Trend ◽  
Healthcare Systems ◽  
Chemical Compositions ◽  
Cancer Therapies ◽  
Pharmacological Effects ◽  
Anticancer Effect ◽  
Anti Cancer ◽  
Tropical Areas ◽  
Cancer Activity

Nowadays, cancer treatment has been a big challenge to healthcare systems. Most of clinical anti-cancer therapies are toxic and cause adverse effects to human body. Therefore, current trend in science is seeking and screening of natural compounds which possess antineoplastic activities to utilize in treatment. Uvaria L. - Annonaceae includes approximately 175 species spreading over tropical areas of Asia, Australia, Africa and America. Studies on chemical compositions and pharmacological effects of Uvaria showed that several compound classes in this genus such as alkaloid, flavonoid, cyclohexen derivaties, acetogenin, steroid, terpenoid, etc. indicate considerable biological activities, for example anti-tumor, anti-cancer, antibacterial, antifungal, antioxidant, etc. Specifically, anti-cancer activity of fractions of extract and pure isolated compounds stands out for cytotoxicity against many cancer cell lines. This study provides an overview of anti-cancer activity of Uvaria and suggests a potential for further studies on seeking and developing novel anti-cancer compounds. Key words: Anti-cancer, Uvaria.

Sign in / Sign up

Export Citation Format

Share Document