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p53 mutation is associated with progression in follicular lymphomas
C A Sander1, T Yano, H M Clark
1Hematopathology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Blood
|October 1, 1993
Summary
Mutations in the p53 tumor suppressor gene are linked to the transformation of low-grade follicular lymphoma into aggressive lymphoma. Detecting p53 abnormalities early may indicate a higher risk of progression.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Follicular lymphoma (FL) is a common indolent non-Hodgkin lymphoma.
- Most FL cases eventually transform into aggressive lymphoma.
- The molecular drivers of this transformation remain largely unknown.
Purpose of the Study:
- To investigate the role of the p53 tumor suppressor gene in the histologic transformation of follicular lymphoma.
- To identify p53 abnormalities in serial biopsies from patients with FL.
Main Methods:
- Studied serial biopsies from 34 patients with transformed FL.
- Utilized immunohistochemistry, single-strand conformation polymorphism (SSCP) analysis, and sequencing to detect p53 abnormalities.
- Analyzed matched pre-transformation low-grade FL biopsies.
Main Results:
- p53 overexpression and mutations were found in 10 of 34 transformed FL cases.
- p53 mutations were present in only 1 of 7 pre-transformation biopsies.
- Rare p53 positive cells were detected in pre-transformation biopsies, with an increase over time in some cases.
- p53 mutations were associated with transformation in 25-30% of FL cases.
- p53 positive low-grade FL showed increased risk for progression.
Conclusions:
- p53 gene mutations are associated with histologic transformation in a significant subset of follicular lymphomas.
- p53 abnormalities can be detected prior to overt histologic transformation.
- Low-grade FL with p53 mutations may warrant aggressive therapeutic approaches due to higher progression risk.