Cancer biology: Charting a tumor's genomic roots

July 17, 2013
Cancer biology: Charting a tumor’s genomic roots
Gastric cancer, caused by infection with the bacterium Helicobacter pylori, is second only to lung cancer as the leading cause of death.

Whole-genome sequencing gives researchers a deeper understanding of factors contributing to the onset and progression of gastric cancer.

By combining the skills and knowledge of a large number of and genomics experts, the Singapore Gastric Cancer Consortium has successfully generated sequences for tumor samples from two patients1. The effort was coordinated by Niranjan Nagarajan, Yijun Ruan and Patrick Tan from the A*STAR Genome Institute of Singapore.

Modern DNA sequencing instruments can deliver a high-quality within a week for less than US$10,000. This technology offers a promising tool for revealing the specific genomic disruptions that underlie poorly understood cancers such as gastric cancer, which remains extremely challenging to diagnose and treat. Unfortunately, the repetitive sequences and large-scale chromosomal rearrangements observed in cancer genomes make it difficult to accurately assemble relatively short DNA sequence 'reads' into a complete sequence.

Nagarajan credits their success to a combination of sophisticated . "We had deep-sequencing data from two complimentary approaches as well as a new assembly approach available to us," he says, "and these provided an ideal test-bed for carrying out this study."

The researchers began by generating genome segments dubbed 'contigs' based on overlap between short sequencing reads. Then they used a long-range called DNA paired-end tag analysis to accurately assemble these into even larger contigs that span a considerable portion of the genome. The resulting coverage allowed them to conduct a detailed census of small-scale sequence alterations as well as larger-scale chromosomal rearrangements. Their work revealed more than five times as many changes than could be detected with more limited conventional sequencing strategies.

Gastric cancer is unusual in that it can be triggered by infection with the Helicobacter pylori. Nagarajan and co-workers' approach allowed them to identify differences between H. pylori- and non-H. pylori-associated cancer cases. "We were able to recover the pathogen genome associated with this cancer from out of massive amounts of sequencing data," says Nagarajan. "We also found a mutational signature that can be linked to infection and is likely to have had a disproportionate impact in tumorigenesis." The researchers were further able to define mutational characteristics that might contribute to specific categories of cancer-related genomic damage, such as unnatural expansion of repetitive sequences or sizeable insertions and deletions.

This work demonstrates the valuable clinical information that tumor genome sequencing can provide. Nagarajan and co-workers are now developing better computational tools that could make better sense of the avalanche of genomic data that can be generated from a single tumor.

Explore further: Researchers identify four distinct mechanisms that contribute to gastric cancers

Related Stories

Researchers identify four distinct mechanisms that contribute to gastric cancers

January 28, 2013
Scientists at A*STAR's Genome Institute of Singapore (GIS) headed a study that discovered four processes by which gastric cancer is formed. This is extremely important since gastric cancer is the second most common cause ...

Computer program identifies rare mutations harbored within diverse populations of cancer cells and microorganisms

April 24, 2013
A tumor is not a uniform mass of identical cells. However, teasing apart genetic heterogeneity within a biopsied tumor can be difficult. Researchers often fail to tell the difference between a rare variant in a DNA dataset ...

Bonanza of genomic sequence data gives researchers valuable new insights into a poorly understood cancer

September 12, 2012
Stomach cancer doesn't get the same publicity as lung or breast cancer, but it is a health threat to be taken very seriously. "Gastric cancer is the second leading cause of worldwide cancer mortality, with an annual death ...

Scientists pair blood test and gene sequencing to detect cancer

November 28, 2012
Scientists at the Johns Hopkins Kimmel Cancer Center have combined the ability to detect cancer DNA in the blood with genome sequencing technology in a test that could be used to screen for cancers, monitor cancer patients ...

Whole genome or exome sequencing: An individual insight

June 27, 2013
Focusing on parts rather than the whole, when it comes to genome sequencing, might be extremely useful, finds research in BioMed Central's open access journal Genome Medicine. The research compares several sequencing technologies ...

Ironing out the link between H. pylori infection and gastric cancer

December 21, 2012
H. pylori frequently causes gastric ulcers and is also one of the greatest risk factors for gastric cancer. H. pylori infection is also associated with another gastric cancer risk factor, iron deficiency.

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.