Mayo Clinic completes first genome-wide analysis of peripheral T-cell lymphomas

Researchers at Mayo Clinic have completed the world's first genome-wide sequencing analysis of peripheral T-cell lymphomas, unlocking the genetic secrets of this poorly understood and highly aggressive cancer of the immune system.

Andrew Feldman, M.D., a Mayo Clinic pathologist and Damon Runyon Clinical Investigator, and a team of researchers affiliated with Mayo's Center for Individualized Medicine and Mayo Clinic Cancer Center, found 13 genomic abnormalities that were seen in multiple peripheral T-cell lymphomas. Of particular interest, five of these abnormalities relate to production and behavior of the -- often called the "guardian of the genome" because of the central role it plays in regulating cell and, therefore, suppressing cancers.

The study, entitled "Genome-wide Analysis Reveals Recurrent Structural Abnormalities of TP63 and other p53-related Genes in Peripheral T-cell Lymphomas," is scheduled for early release in the online edition of the journal Blood on Wednesday, Aug. 1, 2012.

"Every time I diagnose a peripheral T-cell lymphoma, I know that two out of three patients will succumb to that lymphoma," says Dr. Feldman. "That's a very unsatisfying feeling, and I hope that our research can help change those statistics."

Peripheral T-cell lymphomas account for about 12 percent of non-Hodgkin's lymphomas and carry remarkably high . Fewer than 35 percent of patients live five years beyond diagnosis.

New diagnostic (chemical or in the body's system) and treatments aimed at specific subgroups of peripheral T-cell lymphomas could lead to improved outcomes, says Dr. Feldman. Developing these, however, has been a challenge for several reasons. Lymphomas that look remarkably similar under a microscope may differ substantially in their overall prognoses and responses to treatment. Additionally, scientists and doctors have a relatively poor understanding of how peripheral T-cell lymphomas develop and proliferate.

"The most common type of T-cell lymphoma is called 'not otherwise specified.' It's basically a wastebasket diagnosis because we don't understand enough about the specific genetic abnormalities to be able to pinpoint subtypes of T-cell lymphomas that might trigger different treatments by the treating oncologist," says Dr. Feldman.

Dr. Feldman's study will be used to improve diagnostic tests and develop targeted treatments for peripheral T-cell lymphoma.

Among the key findings in the genomic abnormalities of peripheral T-cell lymphoma are:

  • Thirteen recurrent chromosomal rearrangements
  • Five of the 13 rearrangements involve p53-related genes, important for tumor-suppressor function
  • Novel rearrangements involving the TP53 homologue and TP63, which were associated with shortened survival times
  • Four interchromosomal , including the previously known ALK and DUSP22-IRF4 translocations

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