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Concomitant 1p36 deletion and TNFRSF14 mutations in primary cutaneous follicle center lymphoma frequently expressing high levels of EZH2 protein


Primary cutaneous follicle center lymphoma (PCFCL) is an indolent variant of follicular lymphoma (FL) with limited information available on the genetic background of the disease. The genetic hallmark of nodal FL, the t(14;18) translocation, affecting the BCL2 gene, is rare in PCFCL. Loss of 1p36, the most common secondary chromosomal abnormality in nodal FL, has been recently reported in 16.7% of PCFCL cases. In order to further characterize PCFCL, 21 cases were analyzed using interphase fluorescence in situ hybridization with BCL2 break apart and 1p36/1q25 dual color probes. Sanger sequencing was used to investigate TNFRSF14 and EZH2 mutations and immunohistochemistry to assess BCL2, EZH2 protein expressions.

1p36 deletion occurred in 22% (5/21), BCL2 gene break in 10% (2/20) of the PCFCL cases. Mutations of the candidate tumor suppressor gene of the 1p36 region, TNFRSF14 mutations were detected in 4/17 (23.5%) cases with 2 cases presenting with concurrent 1p36 deletion. EZH2 hotspot mutations at Y641, A682, and A692 were not found. High EZH2 protein expression associated with a BCL2 negative phenotype was observed in 43% (9/21) of the cases. BCL2 gene break or 1p36 deletion did not impact the prognosis; however, they showed association with advanced stages at diagnosis (p = 0.016) and a tendency with shorter event free survival (p = 0.052).

In conclusion, 1p36 deletion co-occurs with acquired TNFRSF14 mutations, suggesting a role of this tumor suppressor gene in the development of a subgroup of PCFCL. High EZH2 protein expression associated with BCL2 negative phenotype is common and might represent an ideal therapeutic target.

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This work was funded by the Momentum grant (LP-95021) of the Hungarian Academy of Sciences and the NVKP_16-1-2016-0004 and KH17-126718 grants of the Hungarian National Research, Development and Innovation Office (NKFIH).


This work was funded by the Momentum grant (LP-95021) of the Hungarian Academy of Sciences and the NVKP_16-1-2016-0004 KH17-126718 grants of the Hungarian National Research, Development and Innovation Office (NKFIH).

Author information

MM, EK, TS, and MV have made substantial contributions to acquisition of the data. AG, BB, MV, DK, GP, and JC have made substantial contributions to analysis and interpretation of data. ÁSZ, CB, and AM made substantial contribution to conception and design of the manuscript, and ÁSZ has written the manuscript. AG, BB, MV, DK, GP, JC, and CB conducted cytogenetic, phenotypic, and biologic analyses. All authors have been involved in revising the manuscript and approved the final manuscript.

Correspondence to Ágota Szepesi.

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All protocols were approved by the Institutional Ethical Review Board (TUKEB no. 7/2006).

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The authors declare that they have no conflict of interest.

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Gángó, A., Bátai, B., Varga, M. et al. Concomitant 1p36 deletion and TNFRSF14 mutations in primary cutaneous follicle center lymphoma frequently expressing high levels of EZH2 protein. Virchows Arch 473, 453–462 (2018). https://doi.org/10.1007/s00428-018-2384-3

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  • Primary cutaneous follicle center lymphoma
  • del 1p36
  • TNFRSF14 mutation
  • BCL2
  • EZH2