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Neha Mehta-Shah, MD Photo by Larry Young
Neha Mehta-Shah, MD
Photo by Larry Young

SAN FRANCISCO—An exploratory study suggests cell-free DNA from peripheral blood may be a viable alternative to tumor DNA for mutational profiling in angioimmunoblastic T-cell lymphoma (AITL).

Investigators sequenced cell-free DNA and tumor DNA collected from 13 patients with AITL and found that, in 85% of cases, there was concordance between the tumor mutational profile and the cell-free DNA mutational profile.

“The cell-free DNA mutational analysis seems to mirror the mutational analysis of the tumor in the majority of cases,” said Neha Mehta-Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

“This may be particularly interesting when we don’t have very much tumor DNA available for sequencing, as occurs frequently in this patient population.”

Dr Mehta-Shah presented these findings at the 9th Annual T-cell Lymphoma Forum.

She said the primary objective of this study was to evaluate whether somatic mutation analysis of cell-free DNA for IDH2 correlates with tumor mutational profiling for IDH2.

The secondary objective was to evaluate whether somatic mutational analysis of cell-free DNA mirrors the mutational profile of the tumor.

So Dr Mehta-Shah and her colleagues sequenced various samples from 14 patients with AITL (4 who were newly diagnosed and 10 with relapsed disease).

The investigators compared cell-free DNA obtained from peripheral blood samples with genomic DNA obtained from primary tumor biopsies and with DNA from peripheral blood mononuclear cells (for germline comparison). One of the 14 patients didn’t have tumor tissue available, so 13 patients were included in the analysis.

The team performed targeted next-generation sequencing using Memorial Sloan Kettering Cancer Center’s IMPACT platform, which sequences 410 genes known to be recurrently mutated in cancer.

The investigators observed concordance between the tumor mutational profile and the cell-free DNA profile in 85% of cases (11/13).

Identical alterations in TET2, RHOA, IDH2, DNMT3A, and ROS1 were detected in cell-free DNA from peripheral blood and tumor genomic DNA, with a similar variant allele frequency.

On the other hand, mutational analysis of cell-free DNA obtained from urine samples from 2 of the patients did not correlate with somatic mutations from tumor DNA.

This research also revealed that some samples had multiple mutations in TET2, which are indicative of subclonal populations.

And sequential samples from 2 patients, collected at the start of salvage therapy and at subsequent relapse, showed the disappearance of mutations in RHOA, TET2, and IDH2. This observation has been attributed to clonal evolution and/or changes in overall disease burden.


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