Learn More About the Molecular Diagnostics Service at MSK

VIDEO | 05:30

Go inside the molecular pathology lab, located on the fourth floor of the Arnold and Maria Schwartz Cancer Research Building at MSK. This is where tumor-sequencing tests MSK-IMPACT® and MSK-ACCESS® take place. These tests can help doctors learn important information about individual people’s cancers and help guide their treatment.

Show transcript

Dr. Maria Arcila: Hello everyone, and welcome to the Molecular Diagnostics Laboratory. My name is Dr. Arcila.

I'll be joined by Dr. Marc Ladanyi, who is the Chief of the Molecular Diagnostics Service, and Dr. Ryma Benayed, who is the person who oversees the Next Generation Sequencing Laboratory that we're going to be touring.

Molecular Diagnostics is actually composed of three separate sections: diagnostic molecular pathology, diagnostic molecular genetics, and cytogenetics.

And as a whole, we have been providing service here at MSKCC since the early 1990s. We started as a very small lab, just performing a few hundred assays per year.

And under the leadership of Dr. Marc Ladanyi, we have gone through this very small lab to now testing over 30,000 samples per year. Most of these are high-complexity testing and primarily next-generation sequencing.

Two major assays that we rolled out during this time were MSK-IMPACT® and MSK-ACCESS®. MSK-IMPACT is an assay that was initially created for testing solid tumors and also covering 505 genes that are specifically related to cancer. We also have MSK-ACCESS, which is an assay that is a little smaller and more targeted and covers 129 genes and are highly curated to be able to take care of specific needs of circulating tumor DNA.

The work that we do here is to actually take the DNA fragments from the tissue that was submitted to us, and these are barcoded, and we add specific sequences that are adapters and sequences that are specific to the patient to be able to take that sample through together with many other samples to be tested at the same time. Once the libraries are prepared, they go to the sequencing lab.

So, let's go join Dr. Ryma Benayed who is going to take you through the rest of the process.

Dr. Ryma Benayed: Thank you, Dr. Arcila. We're on the post-area of the Next Generation Sequencing Laboratory. So, the sample libraries are now transferred to a liquid handler called the STARlet, where the libraries are pooled together into a fewer number of tubes. Sample pooling is possible thanks to the unique index sequence that was added to each sample during the library preparation. This is an important step because it allows the simultaneous processing of many samples from different patients into a single run.

After pooling, we end up with individual tubes — DNA tubes representing the whole genome. We have designed capture probes targeting the MSK-IMPACT 505 genes. We also have capture probes for the MSK-ACCESS 129 genes.

Those probes are added to the pool and after a few steps, they are placed on a thermocycler overnight to allow the probes to hybridize the DNA.

The next day, we clean this up, and we're only left with the captured genes of interest from MSK-IMPACT or MSK-ACCESS depending on the protocol.

After sample pooling and capture, we're now ready to set up for sequencing.

This takes place on the NovaSeq 6000 using the S1 flow cells.

For MSK-IMPACT, we can sequence 56 patient matched tumor normal pairs per run, and we do up to six runs a week. For MSK-ACCESS, each NovaSeq run can handle 25 patient matched tumor normal pairs, and we do two to three runs a week.

And now let's hear from our service chief, Dr. Marc Ladanyi.

Dr. Marc Ladanyi: Well, thank you, Dr. Benayed. So, you've heard from Drs. Arcila and Benayed about the streamlining of our clinical NGS operations that's been enabled by this new and expanded space.

I'm very proud that we've assembled the largest group of board-certified molecular pathologists in the country, with the support of the largest group of clinical bioinformaticians of any pathology department in the country, led by Dr. Ahmet Zehir.

Finally, I'm also quite proud that we have the largest Molecular Genetic Pathology Fellowship training program in the country.

Another reason we're very excited about Schwartz-4 is that it allows us to really make progress on several important fronts, including updated and expanded NGS assays for lymphomas and leukemias, whole exome sequencing for very specific germline and somatic applications, and to begin to implement whole genome sequencing.

And in closing, I'd like to extend a special thank you to Dr. DeAngelis for having been such a strong advocate for the renovation of Schwartz-4 to expand our clinical NGS capabilities.