Advances in carcinogenesis: A historical perspective from observational studies to tumor genome sequencing and TP53 mutation spectrum analysis

2011 ◽  
Vol 1816 (2) ◽  
pp. 199-208 ◽  
Author(s):  
Thierry Soussi
Keyword(s):  
Genome Sequencing ◽  
Spectrum Analysis ◽  
Observational Studies ◽  
Historical Perspective ◽  
Tp53 Mutation ◽  
Mutation Spectrum ◽  
Tumor Genome

scholarly journals Improved structural variant interpretation for hereditary cancer susceptibility using long-read sequencing

2020 ◽  
Vol 22 (11) ◽  
pp. 1892-1897 ◽  
Author(s):  
My Linh Thibodeau ◽  
Kieran O’Neill ◽  
Katherine Dixon ◽  
Caralyn Reisle ◽  
Karen L. Mungall ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Hereditary Cancer ◽  
Cancer Susceptibility ◽  
Return Of Results ◽  
Advanced Cancer Patients ◽  
Short Read ◽  
Cancer Susceptibility Genes ◽  
Oxford Nanopore ◽  
Long Read ◽  
Tumor Genome

Abstract Purpose Structural variants (SVs) may be an underestimated cause of hereditary cancer syndromes given the current limitations of short-read next-generation sequencing. Here we investigated the utility of long-read sequencing in resolving germline SVs in cancer susceptibility genes detected through short-read genome sequencing. Methods Known or suspected deleterious germline SVs were identified using Illumina genome sequencing across a cohort of 669 advanced cancer patients with paired tumor genome and transcriptome sequencing. Candidate SVs were subsequently assessed by Oxford Nanopore long-read sequencing. Results Nanopore sequencing confirmed eight simple pathogenic or likely pathogenic SVs, resolving three additional variants whose impact could not be fully elucidated through short-read sequencing. A recurrent sequencing artifact on chromosome 16p13 and one complex rearrangement on chromosome 5q35 were subsequently classified as likely benign, obviating the need for further clinical assessment. Variant configuration was further resolved in one case with a complex pathogenic rearrangement affecting TSC2. Conclusion Our findings demonstrate that long-read sequencing can improve the validation, resolution, and classification of germline SVs. This has important implications for return of results, cascade carrier testing, cancer screening, and prophylactic interventions.

scholarly journals Sensitive and specific post-call filtering of genetic variants in xenograft and primary tumors

2017 ◽  
Author(s):  
Brian K Mannakee ◽  
Uthra Balaji ◽  
Agnieszka K. Witkiewicz ◽  
Ryan N. Gutenkunst ◽  
Erik S. Knudsen
Keyword(s):  
Sensitivity And Specificity ◽  
Genome Sequencing ◽  
Genetic Variants ◽  
Great Promise ◽  
Multiple Sources ◽  
Genome Sequences ◽  
Primary Tumors ◽  
Tumor Genome

AbstractMotivationTumor genome sequencing offers great promise for guiding research and therapy, but spurious variant calls can arise from multiple sources. Mouse contamination can generate many spurious calls when sequencing patient-derived xenografts (PDXs). Paralogous genome sequences can also generate spurious calls when sequencing any tumor. We developed a BLAST-based algorithm, MAPEX, to identify and filter out spurious calls from both these sources.ResultsWhen calling variants from xenografts, MAPEX has similar sensitivity and specificity to more complex algorithms. When applied to any tumor, MAPEX also automatically flags calls that potentially arise from paralogous sequences. Our implementation, mapexr, runs quickly and easily on a desktocomputer. MAPEX is thus a useful addition to almost any pipeline for calling genetic variants in tumors.

scholarly journals Next generation sequencing (NGS) in oncology: lights and shadows

2016 ◽  
Vol 4 (1) ◽  
pp. 17-19
Author(s):  
Margherita Nannini ◽  
Maria A. Pantaleo
Keyword(s):  
Next Generation Sequencing ◽  
Genome Sequencing ◽  
Next Generation ◽  
Coding Regions ◽  
Oncology Research ◽  
Potential Applications ◽  
Functional Consequences ◽  
Next Generation Sequencing Ngs ◽  
Tumor Genome ◽  
Generation Sequencing

Advances in tumor genome sequencing using next generation sequencing (NGS) technologies have facilitated a greater understanding of the genetic abnormalities involved in cancer development and progression, dramatically changing oncology research. There are several different types of NGS technologies. Whole genome sequencing (WGS) determines the sequence of the complete genome, providing information on both coding and non-coding regions and structural variants. However, use is limited by the large volume of data generated, and associated time and resource costs. Whole exome sequencing (WES) determines the sequence of coding regions only, making it faster and cheaper than WGS, and the functional consequences of variants are easier to interpret. However, all variations in non-coding regions are missed. WGS and WES are often used together to maximize detection of variants. A less costly approach is the use of targeted sequencing, which focuses on particular regions of interest, based on their biological relevance. NGS technologies can also be used to sequence RNA, referred to as RNA-Seq. All these NGS technologies, individually or in combination, have a number of potential applications, including identification of biomarkers, and development of diagnostic and therapeutic strategies. However, although advances have been made, there are a number of limitations to be overcome before NGS technologies are routinely applied in both research and clinical practice.

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 TP53 Mutation Spectrum in Smokers and Never Smoking Lung Cancer Patients

2016 ◽  
Vol 07 ◽  
Author(s):  
Ann R. Halvorsen ◽  
Laxmi Silwal-Pandit ◽  
Leonardo A. Meza-Zepeda ◽  
Daniel Vodak ◽  
Phuong Vu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Tp53 Mutation ◽  
Mutation Spectrum ◽  
Lung Cancer Patients

Combined DNA flow cytometry and sorting with k-ras2 mutation spectrum analysis and the prognosis of human sporadic colorectal cancer

Cytometry ◽  
2002 ◽  
Vol 50 (4) ◽  
pp. 216-224 ◽  
Author(s):  
Elio Geido ◽  
Andrea Sciutto ◽  
Alessandra Rubagotti ◽  
Cristina Oliani ◽  
Roberto Monaco ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Flow Cytometry ◽  
Spectrum Analysis ◽  
Mutation Spectrum ◽  
Dna Flow Cytometry ◽  
Sporadic Colorectal Cancer

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.

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