Disruption of chromosomal locus 1p36 differentially modulates TAp73 and ΔNp73 expression in follicular lymphoma

Abstract

The TP73 gene is located at the chromosome 1p36 locus that is commonly disrupted or deleted in follicular lymphoma (FL) with poor prognosis. Therefore, we analyzed the expression of the pro-apoptotic TAp73 and anti-apoptotic ΔNp73 isoforms in cases of FL with normal or abnormal 1p36. We observed a significant increase in ΔNp73 expression and ΔNp73:TAp73 ratio, lower expression of cleaved caspase-3 and a higher frequency of Ki-67 and proliferating cell nuclear antigen (PCNA) positive cells in cases of FL with abnormal 1p36. A negative correlation between the ΔNp73:TAp73 ratio and cleaved caspase-3 expression, and a positive correlation between ΔNp73 expression and Ki-67 or PCNA, were observed. The expression of TAp73 and its pro-apoptotic transcriptional targets BIM. PUMA and NOXA were significantly lower in FL compared to reactive follicular hyperplasia. Together, our data demonstrate that 1p36 disruption is associated with increased ΔNp73 expression, decreased apoptosis and increased proliferation in FL.

Keywords::

• Chromosome 1p36
• p73 isoforms
• follicular lymphoma

Acknowledgements

The study was partly supported by the NIH (UO1 CA84967), Leukemia and Lymphoma Society of America (6032-99), John A. Weibe Jr. Children's Healthcare Foundation (00-02102), University of Nebraska Medical Center Dean's Research Grant and the Cytogenetics Research and Development Fund. Hesham Hassan is supported by the Egyptian Ministry of High Education (Study Abroad Scholarship) and University of Nebraska medical center fellowship.

Potential conflict of interest:

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