ISSN (print) 1997-6933     ISSN (online) 2500-2139
Vol. 16 No. 1 (2023), LYMPHOID TUMORS
Vol. 16 No. 1 (2023)
LYMPHOID TUMORS

Identification of Somatic Mutations in EZH2 Gene and Assessment of Their Prognostic Value in Follicular Lymphoma Grades 1–3А

Published 20.02.2024
Ekaterina Sergeevna Nesterova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
N.A. Severina
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
B.V. Biderman
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
A.B. Sudarikov
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
A.M. Kovrigina
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
T.N. Obukhova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
Ya.K. Mangasarova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
S.M. Kulikov
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
E.E. Zvonkov
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
E.N. Parovichnikova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
V.G. Savchenko
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
2023-1
PDF_2023-16-1_80-87 (Russian)

Keywords

follicular lymphoma
prognosis
bulky
grades
Ki-67
t(14;18)(q32;q21)
EZH2 gene

How to Cite

Nesterova E.S., Severina N.A., Biderman B.V., Sudarikov A.B., Kovrigina A.M., Obukhova T.N., Mangasarova Y.K., Kulikov S.M., Zvonkov E.E., Parovichnikova E.N., Savchenko V.G. Identification of Somatic Mutations in EZH2 Gene and Assessment of Their Prognostic Value in Follicular Lymphoma Grades 1–3А. Clinical Oncohematology. 2024;(1):80–87. doi:10.21320/2500-2139-2023-16-1-80-87.
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Abstract

Aim. To determine the incidence and prognostic value of mutations in exon 16 of EZH2 as well as those of polymorphism с.1582-21А>G (rs2072407) in EZH2 in patients with follicular lymphoma (FL) grades 1–3А in relation to morphologic and cytogenetic tumor characteristics.

Materials & Methods. The prospective cohort study conducted by the National Research Center for Hematology from January 2017 to April 2021 enrolled 80 patients with newly diagnosed FL grades 1/2 and 3А. The median follow-up was 53 months. Molecular and cytogenetic analyses were based on biopsy samples of lymph nodes obtained before chemotherapy. The mutation status of exon 16 in EZH2 and the presence of intronic polymorphism rs2072407 in EZH2 were examined by Sanger sequencing method. Translocation t(14;18)(q32;q21) was detected by karyotyping or FISH.

Results. Mutations in exon 16 of EZH2 (mutEZH2) were identified in 10/80 (13 %) patients. All patients showed missense mutation in codon 646 of EZH2. Translocation t(14;18) was detected in 45/80 (56 %) cases. Poor outcome in the cohort with no t(14;18) was observed 3 times more often than in the group of patients with t(14;18) (p = 0.0001). The presence of t(14;18) was associated with favorable prognosis irrespective of either the mutation status of exon 16 in EZH2 or the FL grade. The analysis of the polymorphism rs2072407 status yielded the following genotypes: AA in 24 % (n = 19), AG in 42 % (n = 34), and GG in 34 % (n = 27) of cases. The variants АА and AG were associated with higher risk of death (hazard ratio 2.9; 95% confidence interval 1.2–10.6; p = 0.01), whereas the genotype GG was associated with wtEZH2 (10 % vs. 37 %) and favorable prognosis (p = 0.065).

Conclusion. Significant biological markers for favorable prognosis in FL appeared to be the presence of t(14;18)(q32;q21) and GG genotype of polymorphism rs2072407 in EZH2. The previously identified prognostic factors (grade 3А, bulky tumor lesions > 6 cm, Ki-67 > 35 %, and a short interval between symptom onset and chemotherapy start) were incorporated into a new unified personalized predictive (index PPI) FL model by supplementing it with two additional biological markers: the presence of t(14;18)(q32;q21) and GG genotype of polymorphism rs2072407. This approach may increase the prognostic value of the new personalized design which will provide the basis for risk-adapted algorithms for FL treatment.

PDF_2023-16-1_80-87 (Russian)

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