January 24, 2018
3 min read

Blood test detects tumor-derived DNA in early-stage cancers

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Jillian Phallen

Researchers at Johns Hopkins Kimmel Cancer Center developed a test that they say identifies several types of cancers in early stages.

Graduate student Jillian Phallen and colleagues obtained blood samples from 200 patients with breast, lung, ovarian or colorectal cancers, and then screened the samples for mutations within 58 genes associated with various cancer types.

A researcher-developed method called targeted error correction sequencing — or TEC-Seq — accurately identified 86 of 138 (62%) stage I and II cancers in the study population.

Among individuals with colon cancer, the test detected cancer-specific DNA in four of eight (50%) patients with stage I disease, eight of nine (89%) with stage II disease, nine of 10 (90%) with stage III disease, and 14 of 15 (93%) with stage IV disease.

Among those with lung cancer, the test accurately detected 13 of 29 (45%) patients with stage I disease, 23 of 32 (72%) with stage II disease, three of four (75%) with stage III disease, and five of six (83%) with stage IV disease.

Among women with ovarian cancer, the test detected 16 of 24 (67%) cases of stage I disease, three of four (75%) cases of stage II disease, six of eight (75%) cases of stage III disease, and five of six (83%) cases of stage IV disease.

Among individuals with breast cancer, the test identified cancer-derived mutations in two of three (67%) women with stage I disease, 17 of 29 (59%) with stage II disease, and in six of 13 (46%) with stage III disease.

HemOnc Today spoke with Phallen about the test, how it differs from other techniques, and what still must be confirmed before the test becomes available for widespread use.


Question: How did you develop this test?

Answer: The TEC-Seq approach is designed to address the need for a very sensitive and highly specific assay that can be used for direct detection of alterations in the blood in patients with early-stage cancers. The goal is early detection. To accomplish this, we developed a liquid biopsy method based on sequencing each position of more than 50 genes, which is about 80,000 bases of the genome. We sequenced each base to a very high depth — more than 30,000 times on average — to identify rare tumor mutations that may be present in the blood. The error correction component of the test is key to establishing the specificity and sensitivity needed to identify the ‘needle in the haystack’ for these types of mutations at early stages.



Q: Can you describe the efficacy and reliability you have seen with this test?

A: So far, the results are very promising. More than half of patients with early-stage breast, colorectal, lung or ovarian cancers were detected using our approach. This bodes well for applying this approach to detect common cancers early. Importantly, the specificity of the approach was very high. We did not detect any alterations among any of the 80,000 bases analyzed in 44 healthy individuals, leading to an extremely high specificity. This is key for early detection.


Q: What differentiates the approach from other liquid biopsy platforms?

A: TEC-Seq was developed specifically with the goal of early detection in mind. It incorporates an error correction pipeline designed to remove false-positive mutation calls and narrow down true, cancer-specific mutations. This is done without relying on knowledge of mutations present in the tumor. This differs from many other liquid biopsy approaches that are focused on late-stage disease or follow alterations in the blood based on already knowing the mutations in the tumor. These types of tests can be very useful for disease monitoring, but, in the setting of screening, there would be no way to predict the alterations to look for in the blood.


Q: What still needs to be confirmed before this approach is used more widely?

A: There is a definite need for larger-scale studies of early cancer detection in a screening setting. This will be necessary to establish the sensitivity and specificity of the test in real-life settings. These studies eventually will move toward implementation of the test in the clinic, which is the ultimate goal.


Q: What is the timeline for possible widespread use?

A: These studies are large orchestrations that involve multiple screening sites and thousands of patients, and they likely will be completed within the next 5 to 7 years.


Q: Is there anything else that you would like to mention?

A: To place our approach and goal of early detection in context, it is important to note that most individuals with cancer are diagnosed at a late stage. We aim to shift the detection of cancer to an earlier stage and apply a detection test in the screening setting. This would be instrumental in moving toward more effective treatments, with improved outcomes and decreased chances for recurrence and disease resistance. – by Jennifer Southall



Phallen J, et al. Sci Transl Med. 2017;doi:10.1126/scitranslmed.aan2415.


For more information:

Jillian Phallen can be reached at The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287; email: jphalle2@jhmi.edu.


Disclosure: Phallen reports no relevant financial disclosures.