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Molecular Testing Guides Diagnosis, Treatment in Blood Cancers

BRIELLE BENYON
Monday, October 19, 2020
As targeted therapies continue to evolve in the cancer space, it is essential for clinicians to understand the basics of genomics, especially when it comes to hematologic malignancies.

“There are many different lymphoma subtypes, and they’re distinguished by their histology, their immune phenotyping, and their underlying genetic abnormalities,” said Eric Hsi, section head of hemapathology and medical director of the automated hematology, flow cytometry, and immunohistochemistry laboratories in the Institute of Pathology and Laboratory Medicine at the Cleveland Clinic.

Hsi recently discussed the basics of blood cancer pathology at the 2020 NCCN Virtual Congress on Hematologic Malignancies.

Types of Molecular Abnormalities


There are 3 types of abnormalities that can occur in a patient’s DNA, Hsi explained. They are:
  • Gene copy number abnormalities: In this situation, clinicians would be looking for gains and losses. These can be detected by routine karyotyping, flourescense in situ hybridization (FISH), DNA microarrays, and next-generation sequencing (NGS).
  • Structural variants: This is known as translocations and rearrangements, and occurs when genes or chromosomes move. This can also show up on routine karyotyping, and FISH tests, as well as PCR-based assays and NGS-based methods.
  • Mutations: When a DNA sequence changes, it can alter the function of that protein. To see if a patient has a genetic mutation, clinicians will conduct Sanger sequencing, allele-specific PCR, or NGS-based methods.

Undergoing molecular testing is crucial for patients with blood cancers, because not only will it give better insight to the type of cancer the patient has, but also what the best treatment regimens may be.

Anaplastic Large Cell Lymphoma


Anaplastic large cell lymphoma (ALCL) is characterized by expression of CD30. However, it is also crucial to know patients’ ALK status, which can be determined by an immunohistochemical test.

“We distinguish positive and negative anaplastic large lymphomas because of the favorable prognosis of positive cases,” Hsi said. “So it’s important to know whether ALK is translocated and overexpressed in these lymphomas.”

ALK-positive ALCL tends to have a much better prognosis than ALK-negative disease, because there are treatments that target ALK, a tyrosine kinase.

Follicular Lymphoma


Patients with follicular lymphoma should also undergo genetic testing. In June, the FDA approved tazemetostat (Tazverik) for relapsed/refractory follicular lymphoma that harbors an EZH2 mutation.

The drug was approved alongside a companion diagnostic test that would determine if a patient has the mutation.

“This is another example of where detecting a molecular abnormality would help us select a therapy,” Hsi said.

Oncology nurses can be advocates in ensuring that their patients undergo the genetic testing that is needed for their disease type and treatment options.

“Molecular testing is routinely used by pathologists for diagnosis, prognosis, and also guiding therapy selection either for targeted or non-targeted therapies,” Hsi said.



 

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