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Q&A: CCMC President Anwar Iqbal on the Future of Cancer Cytogenomics

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Name: Anwar Iqbal

Title: Director of microarray CGH laboratory, department of pathology, University of Rochester Medical Center

Education: PhD, genetics, Osmania University, Hyderabad, India, 1983; MSc, genetics, Osmania University, 1976; BSc, biology, Osmania University, 1974

The third annual meeting of the Cancer Cytogenomics Microarray Consortium, held last week in Chicago, was its largest yet, according to Anwar Iqbal.

Iqbal, who is president of the CCMC, said that the organization now boasts more than 300 members from over 150 organizations in the US and abroad most of whom attended the conference, an exponential increase from the two dozen or so clinical cytogeneticists who met to establish the organization two summers ago.

As an organization, the CCMC is arguably off to a good start. An initial quality control study, that compared the ability of participating laboratories to obtain the same results from the same samples using different array platforms, concluded last year (BAN 12/6/2011). Meantime, American College of Medical Genetics along with CCMC members were involved in drafting guidelines on using microarrays in clinical cancer cytogenetics that are making their way through the approval process of the American College of Medical Genetics.

At the same time, questions loom about the focus of the organization as more researchers adopt next-generation sequencing technologies, and members wrestle with how to best convey the information obtained from arrays and sequencing to clinicians so that they can make treatment decisions.

BioArray News spoke with Iqbal during the CCMC meeting about the organization's focus and future. Below is an edited transcript of that interview.

One issue that has been raised at this meeting is the identity of the organization, and some have even mentioned changing the CCMC's name.

We are thinking about changing the name to be more inclusive of next-generation sequencing. We really don't know where microarrays will be in five years or two years. The emerging tools are changing and now cytogeneticists are in the position to continue offering microarrays and move on to next-gen sequencing. We want to send a message that by changing the name, we are being more inclusive.

What are the aims of the consortium, now that you are in your third year?

At this meeting we have discussed how microarrays should be included as part of clinical trials currently being undertaken on any hematological malignancies or any solid tumors. Chromosomal analysis and and are presently included in clinical trials, but microarrays have not yet been incorporated into standard of care for onclology , as with postnatalgenetics. If microarrays become part of clinical trials, then it becomes simpler for clinicians to access the technology for use in monitoring and treating cancer patients. But even if microarrays are adopted in clinical trials, it may take years to complete the clinical trial. Therefore, it may be valuable to include both microarrays and next gen sequencing in clinical trials.

How will you get arrays into clinical trials? Will you work with drug companies?

That's one way of getting them adopted. There are clinical trial labs, like the University of Rochester Medical Center, that work with pharmaceutical companies. What we can do is that, when a biopharmaceutical company comes to look at our clinical trials, we can show them that microarrays can be used in clinical trials, especially for some specific cancers. So that is one way of doing it.

Another involves multi-institution trials, with different platforms, as was done with the [National Institute of Child Health and Human Development-sponsored] prenatal study, where you had close to 5,000 samples were tested by several institutions (BAN 2/14/2012). This information leads to creating new standards and guidelines.

Are there any plans to secure NIH funding for such a trial?

That is one of the issues we are discussing. Another is how we get the multiple institutions involved. Today was the first time that we showed the results of our own QC trial to the membership, so now they know that we can do much larger studies that can be supported by an NIH grant.

But what would that clinical trial focus on? Would it be for a specific malignancy?

It could be disease specific, like CLL. Or it can go into different hematological malignancies, and come up with a large number of cases from different institutions, CLL, MDS, lymphomas and solid tumors. That can help in bringing some answers to the community.

In terms of guidelines, we were told that they exist but they have not yet been approved by ACMG.

Well, there are a lot of challenges. Not many labs are offering cancer microarrays as a clinical test. A lot of labs are using them in R&D, and only some private and academic labs are offering it as a test. So the test is not being as offered as commonly as a postnatal microarray. A draft of the guidelines have been submitted but must go through the official ACMG process. Some workgroup members, who are also members of the CCMC, authored the draft, but the document needs to be voted on and approved by the Laboratory Quality Assurance Committee of the ACMG, then it goes out for ACMG member comment and final approval must be granted from the Board of Directors of the ACMG. Your labs are among the first adopters of the technology.

Are you seeing more labs moving to cancer cytogenomics?

From the data we have collected from the members, about 45 percent of them are using it as a clinical test. I will add here, that the quality of the presentations [at the meeting] have improved compared to previous years. Even at my center, the clinicians, after years, are using microarrays. It is happening at every institution. They are exploring and adapting microarrays for patient care.

Another issue that has been raised is how to translate array findings into actionable clinical decisions. What is CCMC doing to address that issue?

We have the guidelines coming. They will be very important in how we move from doing what we are doing today, from [traditional] chromosomal analysis, to microarray. [There is also the issue of] new findings, what needs to be informed to the clinician so that the clinician can use that information for patient care. Currently, there are set markers that clinicians are used to, and then with microarrays you get not only those markers, but additional information. The question with the additional findings is what do we do with those. So we need to follow up with those patients, to see in the next year or so what those findings might mean.

Even with established markers, [patients] may have poor prognosis or good prognosis but not everyone with a good prognosis has a good prognosis with treatment. Some of them still relapse – even if they have the same prognosis, same treatment, and they still relapse. There may be some underlying [changes] that microarrays provide additional information. But the clinicians have to be confidant that these new markers are evidence based – and on that basis they will add that marker to the prognostic list.

What do you think participants expected to get out of this meeting?

One of the goals of this meeting was for members to find out what is happening with the consortium. Because many of the members are still in the initial stages of providing microarrays as a clinical test, they wanted to find out about the guidelines, the interpretation, the algorithms, and how to make a correlation between a laboratory finding and a clinical phenotype of the cancer. So those are the challenges that still exist.

What would you like to accomplish by the time of the next summer meeting?

We need to complete our pending projects. The QC trials need to be published. The community needs to know it has been done and is in the public domain. The third thing is that we need to think about having multi-institution clinical trials just like the prenatal groups have done.

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