Genetic Analysis of T-Cell Lymphomas Completed

Nick Mulcahy

August 6, 2012 — The first genome-wide analysis of peripheral T-cell lymphomas has been completed by American researchers.

A team from the Mayo Clinic in Rochester, Minnesota, found 13 genomic abnormalities that are common to peripheral T-cell lymphomas. Five of the genetic abnormalities are related to the p53 protein, which, when it is not mutated, plays a role in suppressing cancers.

The team's study was published online August 1 in the journal Blood.

"Every time I diagnose a peripheral T-cell lymphoma, I know that 2 out of 3 patients will succumb to that lymphoma," said lead author Andrew Feldman, MD, of the Center for Individualized Medicine at the Mayo Clinic, in a press statement. "That's a very unsatisfying feeling, and I hope that my research can help change those statistics."

Peripheral T-cell lymphomas are "aggressive" malignancies with 5-year overall survival rates of about 35%, according to Dr. Feldman and his coauthors.

"Improvement in outcomes has been stymied by poor understanding of the genetics and molecular pathogenesis of peripheral T-cell lymphoma, with a resulting paucity of molecular targets for therapy," they write.

The researchers hope the new genetic information will be used to improve diagnostic tests and develop targeted treatments for peripheral T-cell lymphoma.

Currently, the field of hematologic oncology is somewhat in the dark when diagnosing and treating these lymphomas, suggested Dr. Feldman.

"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 specific subtypes of T-cell lymphomas that might trigger different treatments by the treating oncologist," said Dr. Feldman.

To address the problem, the team developed bioinformatic tools to identify chromosomal rearrangements using genome-wide, next-generation sequencing analysis of DNA libraries. The tools were used to analyze 16 peripheral T-cell lymphoma patient tissue samples and 6 related cell lines.

Of the 5 p53-related genes identified, one abnormality was most common, that of TP63.

TP63 rearrangements were seen in 11/190 (5.8%) of peripheral T-cell lymphoma and were associated with inferior overall survival.

The researchers also highlighted the finding of TP53 mutations but acknowledged that they are "rare" in peripheral T-cell lymphoma compared with other malignancies. "Our findings suggest that a constellation of alternate genetic abnormalities may contribute to disruption of p53-associated tumor suppressor function in PTCL," they write.

The study was supported by a grant from Bernard and Edith Waterman.

Blood. Published online August 1, 2012. Abstract