Advances in understanding cancer genomes through second-generation sequencing

  title={Advances in understanding cancer genomes through second-generation sequencing},
  author={Matthew L Meyerson and S. Gabriel and Gad Getz},
  journal={Nature Reviews Genetics},
Cancers are caused by the accumulation of genomic alterations. Therefore, analyses of cancer genome sequences and structures provide insights for understanding cancer biology, diagnosis and therapy. The application of second-generation DNA sequencing technologies (also known as next-generation sequencing) — through whole-genome, whole-exome and whole-transcriptome approaches — is allowing substantial advances in cancer genomics. These methods are facilitating an increase in the efficiency and… 

Whole genome sequencing analysis for cancer genomics and precision medicine

Explosive advances in next‐generation sequencer (NGS) and computational analyses have enabled exploration of somatic protein‐altered mutations in most cancer types, with coding mutation data

Clinical relevance of cancer genome sequencing.

Advances in next-generation sequencing technologies and sequence enrichment methods are presented in the context of research discovery and both the clinical relevance and challenges associated with the adoption of these genomic technologies in a clinical setting are discussed.

Genomics of AML: clinical applications of next-generation sequencing.

  • J. WelchD. Link
  • Biology
    Hematology. American Society of Hematology. Education Program
  • 2011
How next-generation sequencing is being used to study cancer genomes is discussed, which offers the potential for an individualized approach to treatment in AML and brings us one step closer to personalized medicine.

Cancer whole-genome sequencing: present and future

Analysis of cancer genomes using the present WGS platforms is still primitive and there are substantial improvements to be made in sequencing technologies, informatics and computer resources, so it is also required to analyze much more WGS data and integrate these with multi-omics data, functional data and clinical-pathological data in a large number of sample sets to interpret them more fully and efficiently.

Clinical applications of next-generation sequencing in colorectal cancers.

How NGS-based exome-, whole genome- and methylome-sequencing have extended the understanding of colorectal carcinogenesis is discussed, and the unique genomic features of CRC are introduced, such as the relationship with bacterial pathogens and the massive genomic rearrangements of chromothripsis.

NGS Analysis of Somatic Mutations in Cancer Genomes

Current approaches for the analysis of somatic mutations in cancer genomes using NGS are reviewed, leading to a better understanding of the disease as well as to relevant improvements in the diagnosis and therapy of cancer.

Genomic sequencing for cancer diagnosis and therapy.

What the new findings have taught us about cancer biology are discussed and, more importantly, how these new findings guide more effective diagnostic and treatment strategies are discussed.

Applications of Next-Generation Sequencing in Cancer

The application of NGS technology is reviewed in understanding the underlying goal to catalogue human cancer-causing somatic mutations, which has potential to transform medical practice.

Characterising Somatic Mutations in Cancer Genome by Means of Next‐generation Sequencing

A comprehensive delineation of the somatic mutations in the cancer genome would require WGS of a large number of samples from various cancer types and subtypes, and WGS offers a unique advantage to study structural variants or rearrangements and fusion genes in a single experiment.

Emerging patterns of somatic mutations in cancer

The developing statistical approaches that are used to identify significantly mutated genes are highlighted, and the emerging biological and clinical insights from such analyses are discussed, as well as the future challenges of translating these genomic data into clinical impacts.



Somatic alterations in the human cancer genome.

Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses

It is found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations, which defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors.

A comprehensive catalogue of somatic mutations from a human cancer genome

The genomes of a malignant melanoma and a lymphoblastoid cell line from the same person are sequenced, providing the first comprehensive catalogue of somatic mutations from an individual cancer.


A paired-end sequencing strategy is used to identify somatic rearrangements in breast cancer genomes and provides a new perspective on cancer genomes, highlighting the diversity of somatic upheavals and their potential contribution to cancer development.

The Genomic Landscapes of Human Breast and Colorectal Cancers

It is concluded that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene “mountains” and a much larger number of gene ‘hills’ that are mutated at low frequency.

Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts

Targeted RNA-Seq produces an enhanced view of the molecular state of a set of "high interest" genes by combining next-generation sequencing with capture of sequences from a relevant subset of a transcriptome.

Characterizing the cancer genome in lung adenocarcinoma

A large-scale project to characterize copy-number alterations in primary lung adenocarcinomas using dense single nucleotide polymorphism arrays identifies NKX2-1 (NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung carcinomas.

The Consensus Coding Sequences of Human Breast and Colorectal Cancers

The sequence of well-annotated human protein-coding genes in two common tumor types is determined to define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.

Signatures of mutation and selection in the cancer genome

Structural signatures are derived that distinguish between homozygous deletions over recessive cancer genes and fragile sites and illustrate how structural signatures can be used to distinguish between the influences of mutation and selection in cancer genomes.

High-resolution mapping of copy-number alterations with massively parallel sequencing

A collection of ∼14 million aligned sequence reads from human cell lines has comparable power to detect events as the current generation of DNA microarrays and has over twofold better precision for localizing breakpoints (typically, to within ∼1 kilobase).