UHN’s Laboratory Medicine Program  published Canada’s first study on Optical Genome Mapping used in a clinical setting

In a Canadian first, a team from UHN’s Laboratory Medicine Program (LMP) published a study of a very rare translocation, described using Optical Genome Mapping (OGM). Drs. Peter Molony, Adam Smith, Shamini Selvarajah and Ali Sakhdari published MDS/MPN-Unclassifiable with t(X;17)(q28;q21) and KANSL1-MTCP1/CMC4 Fusion Gene, a study that first described the t(X;17) in MDS/MPN-U and also demonstrated the utility of Optical Genome Mapping to quickly and efficiently characterize this rare translocation using a single assay.

Established Facts:

• MDS/MPN-unclassifiable is a heterogeneous category of diseases.
• Underlying genetic alterations in MDS/MPN-unclassifiable are not well characterized.

Novel Insights:

• This is the first case of MDS/MPN with a t(X;17) translocation leading to KANSL1-MTCP1 and KANSL1-CMC4 fusion genes.
• As in T-PLL, the overexpression of oncogenic protein MTCP1 might have a pathogenic role in myeloid neoplasms.

Bringing Optical Genome Mapping to the forefront of clinical practice

Optical Genome Mapping is a technology that can scan a patient’s genomes for chromosomal rearrangements. The technique works by labelling a specific DNA sequence that repeats about every ~6000 base pairs in the genome. The labelled DNA is run through a nanochannel, separating out individual DNA strands, which are imaged and then assembled against the reference genome to detect all chromosome abnormalities. Karyotyping and FISH are traditional detection approaches with a low resolution. OGM can provide resolution from 150 times to 20,000 times higher than a karyotype analysis, depending on the type of abnormality.

 “The greater the precision we can detect chromosome abnormalities, the better the diagnosis, prognosis and treatment plan will be,” says Dr. Adam Smith, Director of the Cancer Cytogenetics Lab at UHN. “The impact is potentially huge—this is a paradigm shifting technology for cytogenetics.”

By September 2022, UHN will be implementing Optical Genome Mapping as a first line test for certain hematologic malignancies. This will help the team better understand and classify structural variation seen in cancer.

“What we showed in the paper is that we can detect these novel rearrangements at high resolution using a single assay without having to develop custom probes and custom assays to verify what we’re seeing. And we can do it all in one step and do it very quickly and there’s very little subjectivity in this process,” says Dr. Smith.

Moving to OGMs will also support staff by reducing workload and saving time.

“We will no longer have to run >1,000 confirmatory reflex FISH tests each year because OGM gives us a full genome assessment in a single step,” says Dr. Smith.

UHN leading the way

In 2020, Dr. Smith was awarded a Small Research Award, a grant sponsored by LMP’s Research and Innovation Committee, for development of Optimal Genome Mapping in Acute Myeloid Leukemia.  

This allowed the team to begin by analyzing samples with OGM. Now, the team is working through the final phase and validation with a goal of bringing OGMs to the clinical frontline. Once complete, UHN will become the first lab in Canada to introduce this innovative technology into clinical practice.

“Lots of other labs across the country are coming on board now after they’ve seen what we are doing and what’s possible,” says Dr. Smith.

LMP’s cytogenetics team is to continue working with labs from across the globe to finalize international standards and guidelines for interpretation.

 “I’m sure this is just the first of many other interesting findings that this new technology will allow us to discover.”