Disruption of chromosomal locus 1p36 differentially modulates TAp73 and Δnp73 expression in follicular lymphoma

Hesham M. Hassan, Michelle L. Varney, Smrati Jain, Dennis D. Weisenburger, Rakesh K Singh, Bhavana J Dave

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2924-2931
Number of pages8
JournalLeukemia and Lymphoma
Volume55
Issue number12
DOIs
StatePublished - Dec 1 2014

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Follicular Lymphoma
Proliferating Cell Nuclear Antigen
Caspase 3
Hyperplasia
Protein Isoforms
Chromosomes
Apoptosis
Genes

Keywords

  • Chromosome 1p36
  • Follicular lymphoma
  • P73 isoforms

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this

Disruption of chromosomal locus 1p36 differentially modulates TAp73 and Δnp73 expression in follicular lymphoma. / Hassan, Hesham M.; Varney, Michelle L.; Jain, Smrati; Weisenburger, Dennis D.; Singh, Rakesh K; Dave, Bhavana J.

In: Leukemia and Lymphoma, Vol. 55, No. 12, 01.12.2014, p. 2924-2931.

Research output: Contribution to journalArticle

Hassan, Hesham M. ; Varney, Michelle L. ; Jain, Smrati ; Weisenburger, Dennis D. ; Singh, Rakesh K ; Dave, Bhavana J. / Disruption of chromosomal locus 1p36 differentially modulates TAp73 and Δnp73 expression in follicular lymphoma. In: Leukemia and Lymphoma. 2014 ; Vol. 55, No. 12. pp. 2924-2931.
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AB - 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.

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