Detecting chromosomal aberrations in cancer patients using Whole Genome Sequencing

Cancer Diagnostics Using Whole Genome Sequencing

Cancer Diagnostics Using Whole Genome Sequencing

Johns Hopkins researchers have come up yet another application (easy?) of next-gen sequencing. In a paper published in this week’s Science Translational Medicine, titled, “Detection of Chromosomal Alterations in the Circulation of Cancer Patients with Whole-Genome Sequencing”, the team led by Victor Velculescu (including Bert Vogelstein) used whole genome sequencing to detect chromosomal aberrations in cancer patients. The “non-invasive” cancer diagnostic approach might help monitor cancer patients for any cancer recurrence after surgery.  Here is a quick summary of the paper, stay tuned for a review on the data and the methods soon.

Whole Genome Sequencing to Detect Cancer

The rationale behind taking the whole genome sequencing approach is cancer cells have lots of structural variations (chromosomal aberrations), like copy number variations and chromosomal rearrangements, that are not present in the normal cells. And using circulating cell-free DNA as diagnostic sample, one can detect cancer non-invasively.

The team took samples of circulating cell-free DNA from late stage breast (3 samples) and colorectal cancer (7 samples) patients, as well as normal people. They sequenced the DNA using Illumina sequencing technology (GAIIx and HiSeq) and identified a variety of  structural variants, like deletion, duplication, translocation, chromosomal arm gain/loss, that are present in cancer patients, but not in normal people.

The authors detected many chromosomal aberrations that can differentiate cancer patients from normal people, including amplification of known cancer driver genes like ERBB2 and CDK6.

Challenge: Detecting Early Stage Cancer Using Next-Gen Sequencing

This study is more a proof of principle experiment that shows what one can do with whole genome sequencing for cancer diagnostics. The authors say that we need a larger clinical trials to fully show the efficacy such approach in a clinical setting of cancer diagnostics.

The key part of the diagnostic test is the level of circulating tumor DNA in the cancer patients. In this study, authors found that the amount of tumor DNA ranged from 1.4 to 47.9%. The authors also point out that detecting late stage cancer (like this study) is relatively easy as there is a good amount of tumor DNA.

However, detecting early stage cancer will be more challenging as early stage cancer patients typically tend to have small amount of tumor DNA. Thus, early stage cancer diagnostics using sequencing needs greater sequencing depth. The authors hope that with reduced sequencing cost in the future, this approach can be used to detect early stage cancer as well.

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