PPubMed22 Dec 2009Cited 9×

Whole-genome cancer analysis as an approach to deeper understanding of tumour biology Whole-genome cancer analysis

R L Strausberg, A J G Simpson

Abstract

Recent advances in DNA sequencing technology are providing unprecedented opportunities for comprehensive analysis of cancer genomes, exomes, transcriptomes, as well as epigenomic components. The integration of these data sets with well-annotated phenotypic and clinical data will expedite improved interventions based on the individual genomics of the patient and the specific disease.

A figure from Whole-genome cancer analysis as an approach to deeper understanding of tumour biology Whole-genome cancer analysis — fig. from the paper

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Whole-genome and exome sequencing using NextGen technologies reveals extensive somatic alterations, gene fusions, and regulatory mutations, highlighting the need for integrated analysis in cancer research.

What’s new

i.Demonstrated whole-genome sequencing can track somatic alterations and evolution between primary tumors and metastases (e.g., 32 alterations, 11 shared).
ii.Integrated genome and transcriptome analysis uncovered hundreds of RNA‑editing events and highlighted ADAR over‑expression.
iii.Identified eight novel gene‑fusion events in a breast cancer cell line using deep sequencing.
iv.Characterized antisense transcripts for over 6000 human genes, revealing widespread non‑coding activity.
v.Showed dramatic cost reduction for sequencing successive AML genomes, enabling broader application.

How they did it

High‑throughput NextGen platforms (Illumina, 454) were used to sequence whole cancer genomes, exomes, and transcriptomes, often alongside matched normal tissue. The resulting data were integrated with phenotypic and clinical information to assess somatic mutations, copy‑number changes, RNA‑editing, and gene fusions.

What they found

32 somatic alterations detected in the metastasis sample, of which 11 were also present in the primary tumor.
Hundreds of putative RNA‑editing events observed; non‑synonymous edits confirmed in COG3 and SRP9 genes.
Eight novel gene‑fusion events discovered in the HCC1954 breast cancer cell line using ~500,000 454 reads.
Evidence for antisense transcripts found for over 6000 human genes.
The cost of sequencing the second AML genome was dramatically lower than the first despite greater coverage.

Caveats

✕Functional characterization of the many identified variants of unknown significance remains difficult.
✕The biological impact of non‑coding and regulatory alterations is not yet fully understood.
✕Translating genomic findings into effective clinical interventions is still an ongoing challenge.
✕Current studies are limited by the need for larger sample sizes to confirm recurrent events.

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