New technique improves detection of cancer DNA in blood

New approach improves detection of most cancers DNA in blood

New technique improves detection of cancer DNA in blood
Credit score: Ricardo Job-Reese, Broad Communications

A crew led by researchers at Broad Institute of MIT and Harvard, Dana-Farber Most cancers Institute, and Harvard Medical College has developed a brand new methodology to establish hundreds of DNA mutations precisely and effectively in a affected person’s blood pattern with minimal sequencing. The strategy, referred to as MAESTRO, might sooner or later allow the detection of residual most cancers in sufferers who’ve undergone remedy, alerting medical doctors to illness recurrence earlier and extra cheaply than present strategies permit.

“The power to search out uncommon mutations in a medical pattern is beneficial in lots of areas of biomedicine and diagnostics,” defined co-senior writer Viktor Adalsteinsson, affiliate director of the Gerstner Heart for Most cancers Diagnostics on the Broad Institute. “Present strategies require quite a lot of sequencing to search out low-abundance DNA fragments, whereas MAESTRO is delicate sufficient to search out hundreds of mutations with 100 instances much less sequencing.”

The work is printed this week in Nature Biomedical Engineering with further co-senior authors Todd Golub, director of the Broad Institute and college at Dana-Farber Most cancers Institute (DFCI) and Harvard Medical College (HMS), and Michael Makrigiorgos, professor at DFCI and HMS.

Attempting to find most cancers DNA

In a affected person with most cancers, tumor cells shed bits of their DNA into the blood—fragments with telltale mutations indicating they got here from the diseased tissue. However any tumor DNA in a blood pattern is a tiny fraction floating in a sea of wholesome genetic materials. Precisely detecting this sparse quantity of DNA is a problem, particularly when trying to find the small variety of tumor cells left behind after most cancers remedy (referred to as “minimal residual illness,” or MRD).

“We see this want for increased sensitivity,” stated Adalsteinsson. “And our crew has been engaged on quite a few applied sciences to deal with that.”

The crew has beforehand demonstrated success in detecting small quantities of residual most cancers DNA from blood samples by scanning for tons of of most cancers mutations. Scanning for hundreds of mutations can enhance MRD detection charges much more, however this sometimes requires an infinite quantity of sequencing to ship correct outcomes. MAESTRO, which stands for “minor allele enriched sequencing via recognition oligonucleotides,” is a extra environment friendly strategy to detect low-frequency mutations.

How MAESTRO works

To make use of MAESTRO, researchers first sequence a affected person’s tumor biopsy to know the panorama of mutations. With this info in hand, they’ll create specialised molecular probes that may bind to solely these tumor-associated sequences of DNA. Scientists add the molecular probes to the cell-free DNA from blood samples, then wash away any unbound DNA, enabling the sequencing machines to select the uncommon most cancers mutations from the pattern.

On this examine, MAESTRO carried out simply in addition to extra typical sequencing approaches at detecting tons of of low-abundance mutations, uncovering the bulk whereas requiring considerably fewer sources. Moreover, MAESTRO enabled the crew to extend the search to 10,000 mutations at low value, profoundly boosting the detection outcomes.

The researchers additionally reexamined affected person samples that had been analyzed utilizing their earlier strategies. With MAESTRO, they uncovered considerably extra mutations from every examined blood pattern, enhancing the detection of MRD after most cancers remedy.

“MAESTRO combines the benefits of depth and breadth in a single protocol,” stated Makrigiorgos. “This opens up the opportunity of detecting MRD earlier, or figuring out circulating DNA from cancers that shed little or no.”

“This undertaking has been a terrific reminder that new strategies could make DNA sequencing much more highly effective,” added Golub. “It is going to be thrilling to see how MAESTRO can impression fundamental discovery and, sooner or later, medical care.”

Going ahead, the crew is continuous to construct a set of applied sciences that may cut back the fee and improve the sensitivity of most cancers detection, in order that sufferers who may have further remedy to stop recurrence might be recognized sooner.



Extra info:
Gregory Gydush et al, Massively parallel enrichment of low-frequency alleles allows duplex sequencing at low depth, Nature Biomedical Engineering (2022). DOI: 10.1038/s41551-022-00855-9

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