Investigating the frequency of somatic MYD88 L265P mutation in primary ocular adnexal B cell lymphoma.
MYD88 L265P
Allele Specific PCR
B cell Lymphoma
Ocular adnexal lymphoma
Orbital Malignancy
Sanger sequencing
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
09 Sep 2024
09 Sep 2024
Historique:
received:
02
07
2024
accepted:
03
09
2024
medline:
9
9
2024
pubmed:
9
9
2024
entrez:
9
9
2024
Statut:
epublish
Résumé
Ocular adnexal B cell lymphoma is the most common orbital malignancy in adults. Large chromosomal translocations and alterations in cell-signaling pathways were frequently reported in lymphomas. Among the altered pathways, perturbations of NFκB signaling play a significant role in lymphomagenesis. Specifically, the MYD88 L265P mutation, an activator of NFκB signaling, is extensively studied in intraocular lymphoma but not at other sites. Therefore, this study aims to screen the MYD88 L265P mutation in Ocular adnexal B cell lymphoma tumors and assess its clinical significance. Our study of twenty Ocular adnexal B cell lymphoma tumor samples by Allele-Specific Polymerase Chain Reaction identified two samples positive for the MYD88 L265P mutation. Subsequent Sanger sequencing confirmed the presence of the heterozygous mutation in those two samples tested positive in Allele-Specific Polymerase Chain Reaction. A comprehensive review of MYD88 L265P mutation in Ocular adnexal B cell lymphoma revealed variable frequencies, ranging from 0 to 36%. The clinical, pathological, and prognostic features showed no differences between patients with and without the MYD88 L265P mutation. The present study indicates that the MYD88 L265P mutation is relatively infrequent in our cohort, underscoring the need for further validation in additional cohorts.
Sections du résumé
BACKGROUND
BACKGROUND
Ocular adnexal B cell lymphoma is the most common orbital malignancy in adults. Large chromosomal translocations and alterations in cell-signaling pathways were frequently reported in lymphomas. Among the altered pathways, perturbations of NFκB signaling play a significant role in lymphomagenesis. Specifically, the MYD88 L265P mutation, an activator of NFκB signaling, is extensively studied in intraocular lymphoma but not at other sites. Therefore, this study aims to screen the MYD88 L265P mutation in Ocular adnexal B cell lymphoma tumors and assess its clinical significance.
METHODS AND RESULTS
RESULTS
Our study of twenty Ocular adnexal B cell lymphoma tumor samples by Allele-Specific Polymerase Chain Reaction identified two samples positive for the MYD88 L265P mutation. Subsequent Sanger sequencing confirmed the presence of the heterozygous mutation in those two samples tested positive in Allele-Specific Polymerase Chain Reaction. A comprehensive review of MYD88 L265P mutation in Ocular adnexal B cell lymphoma revealed variable frequencies, ranging from 0 to 36%. The clinical, pathological, and prognostic features showed no differences between patients with and without the MYD88 L265P mutation.
CONCLUSION
CONCLUSIONS
The present study indicates that the MYD88 L265P mutation is relatively infrequent in our cohort, underscoring the need for further validation in additional cohorts.
Identifiants
pubmed: 39249595
doi: 10.1007/s11033-024-09903-w
pii: 10.1007/s11033-024-09903-w
doi:
Substances chimiques
Myeloid Differentiation Factor 88
0
MYD88 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
973Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Coupland SE (2014) Ocular and Adnexal Lymphoma: Histopathology. In: Singh AD (ed) Ocular and Adnexal Lymphoma. Berlin Heidelberg, Springer, Berlin, Heidelberg, pp 11–23
doi: 10.1007/978-3-642-38499-8_2
Olsen TG, Heegaard S (2019) Orbital lymphoma. Surv Ophthalmol 64(1):45–66. https://doi.org/10.1016/j.survophthal.2018.08.002
doi: 10.1016/j.survophthal.2018.08.002
pubmed: 30144455
Rovira J, Karube K, Valera A, Colomer D, Enjuanes A, Colomo L et al (2016) MYD88 L265P mutations, but no other variants, identify a subpopulation of DLBCL patients of activated B-cell origin, extranodal involvement, and poor outcome. Clin Cancer Res 22(11):2755–2764. https://doi.org/10.1158/1078-0432.Ccr-15-1525
doi: 10.1158/1078-0432.Ccr-15-1525
pubmed: 26792260
Minderman M, Lantermans H, van der Zwaan C, Hoogendijk AJ, van den Biggelaar M, Kersten MJ et al (2023) The oncogenic human B-cell lymphoma MYD88 L265P mutation genocopies activation by phosphorylation at the Toll/interleukin-1 receptor (TIR) domain. Blood Cancer J 13(1):125. https://doi.org/10.1038/s41408-023-00896-6
doi: 10.1038/s41408-023-00896-6
pubmed: 37591861
pmcid: 10435502
Kraan W, Horlings HM, van Keimpema M, Schilder-Tol EJ, Oud ME, Scheepstra C et al (2013) High prevalence of oncogenic MYD88 and CD79B mutations in diffuse large B-cell lymphomas presenting at immune-privileged sites. Blood Cancer J 3(9):e139. https://doi.org/10.1038/bcj.2013.28
doi: 10.1038/bcj.2013.28
pubmed: 24013661
pmcid: 3789201
Shekhar R, Naseem S, Binota J, Varma N, Malhotra P (2021) Frequency of MYD88 L256P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasm. Hematol Oncol Stem Cell Ther 14(3):231–239. https://doi.org/10.1016/j.hemonc.2020.10.003
doi: 10.1016/j.hemonc.2020.10.003
pubmed: 33217360
Yu X, Li W, Deng Q, Li L, Hsi ED, Young KH et al (2018) MYD88 L265P mutation in lymphoid malignancies. Cancer Res 78(10):2457–2462. https://doi.org/10.1158/0008-5472.CAN-18-0215
doi: 10.1158/0008-5472.CAN-18-0215
pubmed: 29703722
Pham-Ledard A, Beylot-Barry M, Barbe C, Leduc M, Petrella T, Vergier B et al (2014) High frequency and clinical prognostic value of MYD88 L265P mutation in primary cutaneous diffuse large B-cell lymphoma, leg-type. JAMA Dermatol 150(11):1173–1179. https://doi.org/10.1001/jamadermatol.2014.821
doi: 10.1001/jamadermatol.2014.821
pubmed: 25055137
Ren W, Wan H, Own SA, Berglund M, Wang X, Yang M et al (2024) Genetic and transcriptomic analyses of diffuse large B-cell lymphoma patients with poor outcomes within two years of diagnosis. Leukemia 38(3):610–620. https://doi.org/10.1038/s41375-023-02120-7
doi: 10.1038/s41375-023-02120-7
pubmed: 38158444
Weber ANR, Cardona Gloria Y, Çınar Ö, Reinhardt HC, Pezzutto A, Wolz OO (2018) Oncogenic MYD88 mutations in lymphoma: novel insights and therapeutic possibilities. Cancer Immunol Immunother 67(11):1797–1807. https://doi.org/10.1007/s00262-018-2242-9
doi: 10.1007/s00262-018-2242-9
pubmed: 30203262
pmcid: 11028221
Nakamura A, Ohwada C, Takeuchi M, Takeda Y, Tsukamoto S, Mimura N et al (2019) Detection of MYD88 L265P mutation by next-generation deep sequencing in peripheral blood mononuclear cells of Waldenström’s macroglobulinemia and IgM monoclonal gammopathy of undetermined significance. PLoS ONE 14(9):e0221941. https://doi.org/10.1371/journal.pone.0221941
doi: 10.1371/journal.pone.0221941
pubmed: 31483817
pmcid: 6726192
Vela V, Juskevicius D, Gerlach MM, Meyer P, Graber A, Cathomas G et al (2020) High throughput sequencing reveals high specificity of TNFAIP3 mutations in ocular adnexal marginal zone B-cell lymphomas. Hematol Oncol 38(3):284–292. https://doi.org/10.1002/hon.2718
doi: 10.1002/hon.2718
pubmed: 32012328
Zhao A, Wu F, Wang Y, Li J, Xu W, Liu H (2022) Analysis of genetic alterations in ocular adnexal mucosa-associated lymphoid tissue lymphoma with whole-exome sequencing. Front Oncol 12:817635. https://doi.org/10.3389/fonc.2022.817635
doi: 10.3389/fonc.2022.817635
pubmed: 35359413
pmcid: 8962736
Behdad A, Zhou XY, Gao J, Raparia K, Dittman D, Green SJ et al (2019) High frequency of MYD88 L265P mutation in primary ocular adnexal marginal zone lymphoma and its clinicopathologic correlation: a study from a single institution. Arch Pathol Lab Med 143(4):483–493. https://doi.org/10.5858/arpa.2018-0092-OA
doi: 10.5858/arpa.2018-0092-OA
pubmed: 30444439
Kirkegaard MK, Minderman M, Sjo LD, Pals ST, Eriksen PRG, Heegaard S (2023) Prevalence and prognostic value of MYD88 and CD79B mutations in ocular adnexal large B-cell lymphoma: a reclassification of ocular adnexal large B-cell lymphoma. Br J Ophthalmol 107(4):576–581. https://doi.org/10.1136/bjophthalmol-2021-319580
doi: 10.1136/bjophthalmol-2021-319580
pubmed: 34706861
Cani AK, Soliman M, Hovelson DH, Liu CJ, McDaniel AS, Haller MJ et al (2016) Comprehensive genomic profiling of orbital and ocular adnexal lymphomas identifies frequent alterations in MYD88 and chromatin modifiers: new routes to targeted therapies. Mod Pathol 29(7):685–697. https://doi.org/10.1038/modpathol.2016.79
doi: 10.1038/modpathol.2016.79
pubmed: 27102345
pmcid: 4925176
Cascione L, Rinaldi A, Bruscaggin A, Tarantelli C, Arribas AJ, Kwee I et al (2019) Novel insights into the genetics and epigenetics of MALT lymphoma unveiled by next generation sequencing analyses. Haematologica 104(12):e558–e561. https://doi.org/10.3324/haematol.2018.214957
doi: 10.3324/haematol.2018.214957
pubmed: 31018978
pmcid: 6959164
Vela V, Juskevicius D, Dirnhofer S, Menter T, Tzankov A (2022) Mutational landscape of marginal zone B-cell lymphomas of various origin: organotypic alterations and diagnostic potential for assignment of organ origin. Virchows Arch 480(2):403–413. https://doi.org/10.1007/s00428-021-03186-3
doi: 10.1007/s00428-021-03186-3
pubmed: 34494161
Li ZM, Rinaldi A, Cavalli A, Mensah AA, Ponzoni M, Gascoyne RD et al (2012) MYD88 somatic mutations in MALT lymphomas. Br J Haematol 158(5):662–664. https://doi.org/10.1111/j.1365-2141.2012.09176.x
doi: 10.1111/j.1365-2141.2012.09176.x
pubmed: 22640364
Moody S, Thompson JS, Chuang SS, Liu H, Raderer M, Vassiliou G et al (2018) Novel GPR34 and CCR6 mutation and distinct genetic profiles in MALT lymphomas of different sites. Haematologica 103(8):1329–1336. https://doi.org/10.3324/haematol.2018.191601
doi: 10.3324/haematol.2018.191601
pubmed: 29674500
pmcid: 6068028
Yan Q, Wang M, Moody S, Xue X, Huang Y, Bi Y et al (2013) Distinct involvement of NF-κB regulators by somatic mutation in ocular adnexal malt lymphoma. Br J Haematol 160(6):851–854. https://doi.org/10.1111/bjh.12162
doi: 10.1111/bjh.12162
pubmed: 23240725
Moody S, Escudero-Ibarz L, Wang M, Clipson A, Ochoa Ruiz E, Dunn-Walters D et al (2017) Significant association between TNFAIP3 inactivation and biased immunoglobulin heavy chain variable region 4–34 usage in mucosa-associated lymphoid tissue lymphoma. J Pathol 243(1):3–8. https://doi.org/10.1002/path.4933
doi: 10.1002/path.4933
pubmed: 28682481
Zhu D, Ikpatt OF, Dubovy SR, Lossos C, Natkunam Y, Chapman-Fredricks JR et al (2013) Molecular and genomic aberrations in Chlamydophila psittaci negative ocular adnexal marginal zone lymphomas. Am J Hematol 88(9):730–735. https://doi.org/10.1002/ajh.23490
doi: 10.1002/ajh.23490
pubmed: 23720088
pmcid: 3773926
Magistri M, Happ LE, Ramdial J, Lu X, Stathias V, Kunkalla K et al (2021) The genetic landscape of ocular adnexa MALT lymphoma reveals frequent aberrations in NFAT and MEF2B signaling pathways. Cancer Res Commun 1(1):1–16. https://doi.org/10.1158/2767-9764.crc-21-0022
doi: 10.1158/2767-9764.crc-21-0022
pubmed: 35528192
pmcid: 9075502
Johansson P, Klein-Hitpass L, Grabellus F, Arnold G, Klapper W, Pförtner R et al (2016) Recurrent mutations in NF-κB pathway components, KMT2D, and NOTCH1/2 in ocular adnexal MALT-type marginal zone lymphomas. Oncotarget 7(38):62627–62639
doi: 10.18632/oncotarget.11548
pubmed: 27566587
pmcid: 5308752
Johansson P, Klein-Hitpass L, Budeus B, Kuhn M, Lauber C, Seifert M et al (2020) Identifying genetic lesions in ocular adnexal extranodal marginal zone lymphomas of the MALT subtype by whole genome, whole exome and targeted sequencing. Cancers (Basel). https://doi.org/10.3390/cancers12040986
doi: 10.3390/cancers12040986
pubmed: 33339135
Liu F, Karube K, Kato H, Arita K, Yoshida N, Yamamoto K et al (2012) Mutation analysis of NF-kappaB signal pathway-related genes in ocular MALT lymphoma. Int J Clin Exp Pathol 5(5):436–441
pubmed: 22808296
pmcid: 3396059
Martinez-Lopez A, Curiel-Olmo S, Mollejo M, Cereceda L, Martinez N, Montes-Moreno S et al (2015) MYD88 (L265P) somatic mutation in marginal zone B-cell lymphoma. Am J Surg Pathol 39(5):644–651. https://doi.org/10.1097/PAS.0000000000000411
doi: 10.1097/PAS.0000000000000411
pubmed: 25723115
Jung H, Yoo HY, Lee SH, Shin S, Kim SC, Lee S et al (2017) The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP. Oncotarget 8(10):17038–17049
doi: 10.18632/oncotarget.14928
pubmed: 28152507
pmcid: 5370020
Bagratuni T, Ntanasis-Stathopoulos I, Gavriatopoulou M, Mavrianou-Koutsoukou N, Liacos C, Patseas D et al (2018) Detection of MYD88 and CXCR4 mutations in cell-free DNA of patients with IgM monoclonal gammopathies. Leukemia 32(12):2617–2625. https://doi.org/10.1038/s41375-018-0197-7
doi: 10.1038/s41375-018-0197-7
pubmed: 30026568
pmcid: 6286389