Identification and confirmation via in situ hybridization of Merkel cell polyomavirus in rare cases of posttransplant cutaneous T-cell lymphoma.
MCPyV
Merkel cell polyomavirus
PTLD
fMF
mycosis fungoides
Journal
Journal of cutaneous pathology
ISSN: 1600-0560
Titre abrégé: J Cutan Pathol
Pays: United States
ID NLM: 0425124
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
revised:
25
05
2023
received:
31
08
2022
accepted:
06
06
2023
medline:
14
8
2023
pubmed:
3
7
2023
entrez:
3
7
2023
Statut:
ppublish
Résumé
Viral infection is an oncogenic factor in many hematolymphoid malignancies. We sought to determine the diagnostic yield of aligning off-target reads incidentally obtained during targeted hematolymphoid next-generation sequencing to a large database of viral genomes to screen for viral sequences within tumor specimens. Alignment of off-target reads to viral genomes was performed using magicBLAST. Localization of Merkel cell polyomavirus (MCPyV) RNA was confirmed by RNAScope in situ hybridization. Integration analysis was performed using Virus-Clip. Four cases of post-cardiac-transplant folliculotropic mycosis fungoides (fMF) and one case of peripheral T-cell lymphoma (PTCL) were positive in off-target reads for MCPyV DNA. Two of the four cases of posttransplant fMF and the case of PTCL showed localization of MCPyV RNA to malignant lymphocytes, whereas the remaining two cases of posttransplant fMF showed MCPyV RNA in keratinocytes. Our findings raise the question of whether MCPyV may play a role in rare cases of T-lymphoproliferative disorders, particularly in the skin and in the heavily immunosuppressed posttransplant setting.
Sections du résumé
BACKGROUND
BACKGROUND
Viral infection is an oncogenic factor in many hematolymphoid malignancies. We sought to determine the diagnostic yield of aligning off-target reads incidentally obtained during targeted hematolymphoid next-generation sequencing to a large database of viral genomes to screen for viral sequences within tumor specimens.
METHODS
METHODS
Alignment of off-target reads to viral genomes was performed using magicBLAST. Localization of Merkel cell polyomavirus (MCPyV) RNA was confirmed by RNAScope in situ hybridization. Integration analysis was performed using Virus-Clip.
RESULTS
RESULTS
Four cases of post-cardiac-transplant folliculotropic mycosis fungoides (fMF) and one case of peripheral T-cell lymphoma (PTCL) were positive in off-target reads for MCPyV DNA. Two of the four cases of posttransplant fMF and the case of PTCL showed localization of MCPyV RNA to malignant lymphocytes, whereas the remaining two cases of posttransplant fMF showed MCPyV RNA in keratinocytes.
CONCLUSIONS
CONCLUSIONS
Our findings raise the question of whether MCPyV may play a role in rare cases of T-lymphoproliferative disorders, particularly in the skin and in the heavily immunosuppressed posttransplant setting.
Substances chimiques
DNA, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
835-844Subventions
Organisme : Private research grant
Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Marques-Piubelli ML, Salas YI, Pachas C, Becker-Hecker R, Vega F, Miranda RN. Epstein-Barr virus-associated B-cell lymphoproliferative disorders and lymphomas: a review. Pathology (Phila). 2020;52(1):40-52. doi:10.1016/j.pathol.2019.09.006
Quintanilla-Martinez L, Swerdlow SH, Tousseyn T, Barrionuevo C, Nakamura S, Jaffe ES. New concepts in EBV-associated B, T, and NK cell lymphoproliferative disorders. Virchows Arch. 2023;482(1):227-244. doi:10.1007/s00428-022-03414-4
Campo E, Jaffe ES, Cook JR, et al. The international consensus classification of mature lymphoid neoplasms: a report from the clinical advisory committee. Blood. 2022;140(11):1229-1253. doi:10.1182/blood.2022015851
Zuo X, Zhou R, Yang S, Ma G. HTLV-1 persistent infection and ATLL oncogenesis. J Med Virol. 2023;95(1):e28424. doi:10.1002/jmv.28424
Rodríguez-Caballero A, García-Montero AC, Bárcena P, et al. Expanded cells in monoclonal TCR-αβ+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis recognize hCMV antigens. Blood. 2008;112(12):4609-4616. doi:10.1182/blood-2008-03-146241
Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319(5866):1096-1100. doi:10.1126/science.1152586
Andres C, Puchta U, Sander CA, Ruzicka T, Flaig MJ. Prevalence of Merkel cell polyomavirus DNA in cutaneous lymphomas, pseudolymphomas, and inflammatory skin diseases. Am J Dermatopathol. 2010;32(6):593-598. doi:10.1097/DAD.0b013e3181ce8beb
Mirvish ED, Pomerantz RG, Geskin LJ. Infectious agents in cutaneous T-cell lymphoma. J Am Acad Dermatol. 2011;64(2):423-431. doi:10.1016/j.jaad.2009.11.692
Kreuter A, Silling S, Dewan M, Stücker M, Wieland U. Evaluation of 4 recently discovered human polyomaviruses in primary cutaneous B-cell and T-cell lymphoma. Arch Dermatol. 2011;147(12):1449-1451. doi:10.1001/archdermatol.2011.330
Murakami I, Matsushita M, Iwasaki T, et al. High viral load of Merkel cell polyomavirus DNA sequences in Langerhans cell sarcoma tissues. Infect Agent Cancer. 2014;9:15. doi:10.1186/1750-9378-9-15
Hirahata M, Abe T, Tanaka N, et al. Genome information broker for viruses (GIB-V): database for comparative analysis of virus genomes. Nucleic Acids Res. 2007;35:D339-D342. doi:10.1093/nar/gkl1004
Boratyn GM, Thierry-Mieg J, Thierry-Mieg D, Busby B, Madden TL. Magic-BLAST, an accurate RNA-seq aligner for long and short reads. BMC Bioinformatics. 2019;20(1):405. doi:10.1186/s12859-019-2996-x
Bowman AS. Identification of viral integration sites in cancer genomes using unmapped reads in targeted next-generation sequencing data. Paper presented at: Association for Molecular Pathology Annual Meeting, 2018. 2018.
Camacho C, Coulouris G, Avagyan V, et al. BLAST+: architecture and applications. BMC Bioinformatics. 2009;10:421. doi:10.1186/1471-2105-10-421
National Center for Biotechnology Information. Standard Nucleotide BLAST. Accessed May 21, 2021. https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastn&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome
Ho DWH, Sze KMF, Ng IOL. Virus-Clip: a fast and memory-efficient viral integration site detection tool at single-base resolution with annotation capability. Oncotarget. 2015;6(25):20959-20963. doi:10.18632/oncotarget.4187
Wang L, Harms PW, Palanisamy N, et al. Age and gender associations of virus positivity in Merkel cell carcinoma characterized using a novel RNA in situ hybridization assay. Clin Cancer Res. 2017;23(18):5622-5630. doi:10.1158/1078-0432.CCR-17-0299
Narayanan D, Rady PL, Tyring SK. Recent developments in trichodysplasia spinulosa disease. Transpl Infect Dis. 2020;22(6):e13434. doi:10.1111/tid.13434
Lawrence LEB, Saleem A, Sahoo MK, et al. Is Merkel cell carcinoma of lymph node actually metastatic cutaneous merkel cell carcinoma? Am J Clin Pathol. 2020;154(3):369-380. doi:10.1093/ajcp/aqaa051
Wang L, Yang JK, Kabaleeswaran V, et al. The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations. Nat Struct Mol Biol. 2010;17(11):1324-1329. doi:10.1038/nsmb.1920
Kataoka K, Miyoshi H, Sakata S, et al. Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas. Leukemia. 2019;33(7):1687-1699. doi:10.1038/s41375-019-0380-5
Fabrizio FP, Trombetta D, Rossi A, Sparaneo A, Castellana S, Muscarella LA. Gene code CD274/PD-L1: from molecular basis toward cancer immunotherapy. Ther Adv Med Oncol. 2018;10:1758835918815598. doi:10.1177/1758835918815598
Czech-Sioli M, Günther T, Therre M, et al. High-resolution analysis of Merkel cell polyomavirus in Merkel cell carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms. PLoS Pathog. 2020;16(8):e1008562. doi:10.1371/journal.ppat.1008562
Starrett GJ, Thakuria M, Chen T, et al. Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma. Genome Med. 2020;12(1):30. doi:10.1186/s13073-020-00727-4
Goh G, Walradt T, Markarov V, et al. Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy. Oncotarget. 2016;7(3):3403-3415. doi:10.18632/oncotarget.6494
Mansour S, Connell F, Steward C, et al. Emberger syndrome-primary lymphedema with myelodysplasia: report of seven new cases. Am J Med Genet A. 2010;152A(9):2287-2296. doi:10.1002/ajmg.a.33445
Vinh DC, Patel SY, Uzel G, et al. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood. 2010;115(8):1519-1529. doi:10.1182/blood-2009-03-208629
Sekhar M, Pocock R, Lowe D, et al. Can somatic GATA2 mutation mimic germ line GATA2 mutation? Blood Adv. 2018;2(8):904-908. doi:10.1182/bloodadvances.2017012617
Alfayez M, Wang SA, Bannon SA, et al. Myeloid malignancies with somatic GATA2 mutations can be associated with an immunodeficiency phenotype. Leuk Lymphoma. 2019;60(8):2025-2033. doi:10.1080/10428194.2018.1551535
Vedula RS, Cheng MP, Ronayne CE, et al. Somatic GATA2 mutations define a subgroup of myeloid malignancy patients at high risk for invasive fungal disease. Blood Adv. 2021;5(1):54-60. doi:10.1182/bloodadvances.2020002854
Koljonen V, Sahi H, Böhling T, Mäkisalo H. Post-transplant Merkel cell carcinoma. Acta Derm Venereol. 2016;96(4):442-447. doi:10.2340/00015555-2284
Shuda M, Arora R, Kwun HJ, et al. Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int J Cancer. 2009;125(6):1243-1249. doi:10.1002/ijc.24510
Gormley RH, Kim EJ, Rook AH, et al. Merkel cell polyomavirus in low levels in folliculotropic mycosis fungoides represents a passenger, not a driver. Int J Dermatol. 2015;54(5):e182-e183. doi:10.1111/ijd.12754
Tolstov YL, Knauer A, Chen JG, et al. Asymptomatic primary Merkel cell polyomavirus infection among adults. Emerg Infect Dis. 2011;17(8):1371-1380. doi:10.3201/eid1708.110079
Liu W, Yang R, Payne AS, et al. Identifying the target cells and mechanisms of Merkel cell polyomavirus infection. Cell Host Microbe. 2016;19(6):775-787. doi:10.1016/j.chom.2016.04.024
Schowalter RM, Reinhold WC, Buck CB. Entry tropism of BK and Merkel cell polyomaviruses in cell culture. PloS One. 2012;7(7):e42181. doi:10.1371/journal.pone.0042181
Toracchio S, Foyle A, Sroller V, et al. Lymphotropism of Merkel cell polyomavirus infection, Nova Scotia, Canada. Emerg Infect Dis. 2010;16(11):1702-1709. doi:10.3201/eid1611.100628
Peretti A, Borgogna C, Rossi D, et al. Analysis of human β-papillomavirus and Merkel cell polyomavirus infection in skin lesions and eyebrow hair bulbs from a cohort of patients with chronic lymphocytic leukaemia. Br J Dermatol. 2014;171(6):1525-1528. doi:10.1111/bjd.13215
Paus R, Ito N, Takigawa M, Ito T. The hair follicle and immune privilege. J Investig Dermatol Symp Proc. 2003;8(2):188-194. doi:10.1046/j.1087-0024.2003.00807.x
Bertolini M, McElwee K, Gilhar A, Bulfone-Paus S, Paus R. Hair follicle immune privilege and its collapse in alopecia areata. Exp Dermatol. 2020;29(8):703-725. doi:10.1111/exd.14155
Zhao J, Jia Y, Shen S, et al. Merkel cell polyomavirus small T antigen activates noncanonical NF-κB signaling to promote tumorigenesis. Mol Cancer Res. 2020;18(11):1623-1637. doi:10.1158/1541-7786.MCR-20-0587
Griffiths DA, Abdul-Sada H, Knight LM, et al. Merkel cell polyomavirus small T antigen targets the NEMO adaptor protein to disrupt inflammatory signaling. J Virol. 2013;87(24):13853-13867. doi:10.1128/JVI.02159-13
Chang TP, Vancurova I. NFκB function and regulation in cutaneous T-cell lymphoma. Am J Cancer Res. 2013;3(5):433-445.
Leitenberger JJ, Abdelmalek M, Wang RC, Strasfeld L, Hopkins RS. Two cases of trichodysplasia spinulosa responsive to compounded topical cidofovir 3% cream. JAAD Case Rep. 2015;1(6):S33-S35. doi:10.1016/j.jdcr.2015.09.019
Tristram A, Fiander A. Clinical responses to cidofovir applied topically to women with high grade vulval intraepithelial neoplasia. Gynecol Oncol. 2005;99(3):652-655. doi:10.1016/j.ygyno.2005.07.127
Sendagorta E, Bernardino JI, Álvarez-Gallego M, et al. Topical cidofovir to treat high-grade anal intraepithelial neoplasia in HIV-infected patients: a pilot clinical trial. AIDS. 2016;30(1):75-82. doi:10.1097/QAD.0000000000000886
Tristram A, Hurt CN, Madden T, et al. Activity, safety, and feasibility of cidofovir and imiquimod for treatment of vulval intraepithelial neoplasia (RT3VIN): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2014;15(12):1361-1368. doi:10.1016/S1470-2045(14)70456-5
Stier EA, Goldstone SE, Einstein MH, et al. Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women. AIDS. 2013;27(4):545-551. doi:10.1097/QAD.0b013e32835a9b16