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01-01-2019 | Short Communication

Candidate susceptibility variants in angioimmunoblastic T-cell lymphoma

Authors: Iikki Donner, Riku Katainen, Eevi Kaasinen, Mervi Aavikko, Lauri J. Sipilä, Eero Pukkala, Lauri A. Aaltonen

Published in: Familial Cancer | Issue 1/2019

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma with a poor prognosis: the 5-year survival rate is approximately 30%. Somatic driver mutations have been found in TET2, IDH2, DNMT3A, RHOA, FYN, PLCG1, and CD28, whereas germline susceptibility to AITL has to our knowledge not been studied. The homogenous Finnish population is well suited for studies on genetic predisposition. Here, we performed an exome-wide rare variant analysis in 23 AITL patients. No germline mutations were found in the driver genes, implying that they are not frequently involved in genetic AITL predisposition. Potentially pathogenic variants present in at least two patients and showing significant (p < 0.01) enrichment in our sample set were found in ten genes: POLK, PRKCB, ZNF676, PRRC2B, PCDHGB6, GNL3L, TTC36, OTOG, OSGEPL1, and RASSF9. The most significantly enriched variants, causing p.Lys469Ter in a splice variant of POLK and p.Pro588His in PRKCB, are intriguing candidates as Polk deficient mice display a spontaneous mutator phenotype, whereas PRKCB was recently shown to be somatically mutated in 33% of another peripheral T-cell lymphoma, adult T-cell lymphoma. If validated, our findings would provide new insight into the pathogenesis of AITL, as well as tools for early detection in susceptible individuals.

Federico M, Rudiger T, Bellei M, Nathwani BN, Luminari S, Coiffier B, Harris NL, Jaffe ES, Pileri SA, Savage KJ, Weisenburger DD, Armitage JO, Mounier N, Vose JM (2013) Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol 31:240–246CrossRefPubMed

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon

de Leval L, Rickman DS, Thielen C, Reynies AD, Huang YL, Delsol G, Lamant L, Leroy K, Brière J, Molina T, Berger F, Gisselbrecht C, Xerri L, Gaulard P (2007) The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood 109:4952–4963CrossRefPubMed

Rochford R, Moormann AM (2015) Burkitt’s lymphoma. In: Münz C (ed) Epstein Barr virus, vol 1. Springer, Cham

Zhou Y, Attygalle AD, Chuang SS, Diss T, Ye H, Liu H, Hamoudi RA, Munson P, Bacon CM, Dogan A, Du MQ (2007) Angioimmunoblastic T-cell lymphoma: histological progression associates with EBV and HHV6B viral load. Br J Haematol 138:44–53CrossRefPubMed

Chen YP, Jones D, Chen TY, Chang KC (2014) Epstein-Barr virus present in T cells or B cells shows differential effects on hemophagocytic symptoms associated with outcome in T-cell lymphomas. Leuk Lymphoma 55:2038–2047CrossRefPubMed

Lemonnier F, Couronné L, Parrens M, Jaïs JP, Travert M, Lamant L, Tournillac O, Rousset T, Fabiani B, Cairns RA, Mak T, Bastard C, Bernard OA, de Leval L, Gaulard P (2012) Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood 120:1466–1469CrossRefPubMed

Odejide O, Weigert O, Lane AA, Toscano D, Lunning MA, Kopp N, Kim S, van Bodegom D, Bolla S, Schatz JH, Teruya-Feldstein J, Hochberg E, Louissaint A, Dorfman D, Stevenson K, Rodig SJ, Piccaluga PP, Jacobsen E, Pileri SA, Harris NL, Ferrero S, Inghirami G, Horwitz SM, Weinstock DM (2014) A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood 123:1293–1296CrossRefPubMedPubMedCentral

Cairns RA, Iqbal J, Lemonnier F, Kucuk C, de Leval L, Jais JP, Parrens M, Martin A, Xerri L, Brousset P, Chan LC, Chan WC, Gaulard P, Mak TW (2012) IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood 119:1901–1903CrossRefPubMedPubMedCentral

10.

Wang C, McKeithan TW, Gong Q, Zhang W, Bouska A, Rosenwald A, Gascoyne RD, Wu X, Wang J, Muhammad Z, Jiang B, Rohr J, Cannon A, Steidl C, Fu K, Li Y, Hung S, Weisenburger DD, Greiner TC, Smith L, Ott G, Rogan EG, Staudt LM, Vose J, Iqbal J, Chan WC (2015) IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma. Blood 126:1741–1752CrossRefPubMedPubMedCentral

11.

Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC, McMichael JF, Schmidt HK, Yellapantula V, Miller CA, Ozenberger BA, Welch JS, Link DC, Walter MJ, Mardis ER, Dipersio JF, Chen F, Wilson RK, Ley TJ, Ding L (2014) Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 20:1472–1478CrossRefPubMedPubMedCentral

12.

Palomero T, Couronné L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, Carpenter Z, Abate F, Allegretta M, Haydu JE, Jiang X, Lossos IS, Nicolas C, Balbin M, Bastard C, Bhagat G, Piris MA, Campo E, Bernard OA, Rabadan R, Ferrando AA (2014) Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet 46:166–170CrossRefPubMedPubMedCentral

13.

Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y, Muto H, Tsuyama N, Sato-Otsubo A, Okuno Y, Sakata S, Kamada Y, Nakamoto-Matsubara R, Tran NB, Izutsu K, Sato Y, Ohta Y, Furuta J, Shimizu S, Komeno T, Sato Y, Ito T, Noguchi M, Noguchi E, Sanada M, Chiba K, Tanaka H, Suzukawa K, Nanmoku T, Hasegawa Y, Nureki O, Miyano S, Nakamura N, Takeuchi K, Ogawa S, Chiba S (2014) Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet 46:171–175CrossRefPubMed

14.

Vallois D, Dobay MP, Morin RD, Lemonnier F, Missiaglia E, Juilland M, Iwaszkiewicz J, Fataccioli V, Bisig B, Roberti A, Grewal J, Bruneau J, Fabiani B, Martin A, Bonnet C, Michielin O, Jais JP, Figeac M, Bernard OA, Delorenzi M, Haioun C, Tournilhac O, Thome M, Gascoyne RD, Gaulard P, de Leval L (2016) Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas. Blood 128:1490–1502CrossRefPubMed

15.

Rohr J, Guo S, Huo J, Bouska A, Lachel C, Li Y, Simone PD, Zhang W, Gong Q, Wang C, Cannon A, Heavican T, Mottok A, Hung S, Rosenwald A, Gascoyne R, Fu K, Greiner TC, Weisenburger DD, Vose JM, Staudt LM, Xiao W, Borgstahl GE, Davis S, Steidl C, McKeithan T, Iqbal J, Chan WC (2016) Recurrent activating mutations of CD28 in peripheral T-cell lymphomas. Leukemia 30:1062–1070CrossRefPubMed

16.

Pukkala E, Engholm G, Højsgaard Schmidt LK, Storm H, Khan S, Lambe M, Pettersson D, Ólafsdóttir E, Tryggvadóttir L, Hakanen T, Malila N, Virtanen A, Johannesen TB, Larønningen S, Ursin G. 2018. Nordic Cancer Registries—an overview of their procedures and data comparability. Acta Oncol 57:440–455CrossRefPubMed

17.

Donner I, Katainen R, Tanskanen T, Kaasinen E, Aavikko M, Ovaska K, Artama M, Pukkala E, Aaltonen LA (2017) Candidate susceptibility variants for esophageal squamous cell carcinoma. Genes Chromosom Cancer 56:453–459CrossRefPubMed

18.

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O’Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG (2016) Analysis of protein-coding genetic variation in 60,706 humans. Exome Aggreg Consort Nature 536:285–291

19.

Choi Y, Chan AP (2015) PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics 31:2745–2747CrossRefPubMedPubMedCentral

20.

Kumar P, Henikoff S, Ng PC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4:1073–1081CrossRefPubMed

21.

Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7:248–249CrossRefPubMedPubMedCentral

22.

Washington MT, Minko IG, Johnson RE, Wolfle WT, Harris TM, Lloyd RS, Prakash S, Prakash L (2004) Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases iota and kappa. Mol Cell Biol 24:5687–5693CrossRefPubMedPubMedCentral

23.

Stancel JN, McDaniel LD, Velasco S, Richardson J, Guo C, Friedberg EC (2009) Polk mutant mice have a spontaneous mutator phenotype. DNA Repair 8:1355–1362CrossRefPubMedPubMedCentral

24.

Abrams ST, Lakum T, Lin K, Jones GM, Treweeke AT, Farahani M, Hughes M, Zuzel M, Slupsky JR (2007) B-cell receptor signaling in chronic lymphocytic leukemia cells is regulated by overexpressed active protein kinase CbetaII. Blood 109:1193–1201CrossRefPubMed

25.

Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T, Yasunaga J, Totoki Y, Chiba K, Sato-Otsubo A, Nagae G, Ishii R, Muto S, Kotani S, Watatani Y, Takeda J, Sanada M, Tanaka H, Suzuki H, Sato Y, Shiozawa Y, Yoshizato T, Yoshida K, Makishima H, Iwanaga M, Ma G, Nosaka K, Hishizawa M, Itonaga H, Imaizumi Y, Munakata W, Ogasawara H, Sato T, Sasai K, Muramoto K, Penova M, Kawaguchi T, Nakamura H, Hama N, Shide K, Kubuki Y, Hidaka T, Kameda T, Nakamaki T, Ishiyama K, Miyawaki S, Yoon SS, Tobinai K, Miyazaki Y, Takaori-Kondo A, Matsuda F, Takeuchi K, Nureki O, Aburatani H, Watanabe T, Shibata T, Matsuoka M, Miyano S, Shimoda K, Ogawa S (2015) Integrated molecular analysis of adult T cell leukemia/lymphoma. Nat Genet 47:1304–1315CrossRefPubMed

26.

Antal CE, Hudson AM, Kang E, Zanca C, Wirth C, Stephenson NL, Trotter EW, Gallegos LL, Miller CJ, Furnari FB, Hunter T, Brognard J, Newton AC (2015) Cancer-associated protein kinase C mutations reveal kinase’s role as tumor suppressor. Cell 160:489–502CrossRefPubMedPubMedCentral

27.

Mangino M, Hwang SJ, Spector TD, Hunt SC, Kimura M, Fitzpatrick AL, Christiansen L, Petersen I, Elbers CC, Harris T, Chen W, Srinivasan SR, Kark JD, Benetos A, El Shamieh S, Visvikis-Siest S, Christensen K, Berenson GS, Valdes AM, Viñuela A, Garcia M, Arnett DK, Broeckel U, Province MA, Pankow JS, Kammerer C, Liu Y, Nalls M, Tishkoff S, Thomas F, Ziv E, Psaty BM, Bis JC, Rotter JI, Taylor KD, Smith E, Schork NJ, Levy D, Aviv A (2012) Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Hum Mol Genet 21:5385–5394CrossRefPubMedPubMedCentral

28.

Do SK, Yoo SS, Choi YY, Choi JE, Jeon HS, Lee WK, Lee SY, Lee J, Cha SI, Kim CH, Park JY (2015) Replication of the results of genome-wide and candidate gene association studies on telomere length in a Korean population. Korean J Intern Med 30:719–726CrossRefPubMedPubMedCentral

29.

Du X, Rao MR, Chen XQ, Wu W, Mahalingam S, Balasundaram D (2006) The homologous putative GTPases Grn1p from fission yeast and the human GNL3L are required for growth and play a role in processing of nucleolar pre-rRNA. Mol Biol Cell 17:460–474CrossRefPubMedPubMedCentral

30.

Zhu Q, Meng L, Hsu JK, Lin T, Teishima J, Tsai RY (2009) GNL3L stabilizes the TRF1 complex and promotes mitotic transition. J Cell Biol 185:827–839CrossRefPubMedPubMedCentral

31.

Okamoto N, Yasukawa M, Nguyen C, Kasim V, Maida Y, Possemato R, Shibata T, Ligon KL, Fukami K, Hahn WC, Masutomi K (2011) Maintenance of tumor initiating cells of defined genetic composition by nucleostemin. Proc Natl Acad Sci USA 108:20388–20393CrossRefPubMedPubMedCentral

32.

Thoompumkal IJ, Rehna K, Anbarasu K, Mahalingam S (2016) Leucine Zipper Down-regulated in Cancer-1 (LDOC1) interacts with Guanine nucleotide binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-κB) signaling during cell proliferation. Cell Cycle 15:3251–3267CrossRefPubMedPubMedCentral

33.

Chen L, Johnson RC, Milgram SL (1998) P-CIP1, a novel protein that interacts with the cytosolic domain of peptidylglycine alpha-amidating monooxygenase, is associated with endosomes. J Biol Chem 273:33524–33532CrossRefPubMed

34.

Rodriguez-Viciana P, Sabatier C, McCormick F (2004) Signaling specificity by Ras family GTPases is determined by the full spectrum of effectors they regulate. Mol Cell Biol 24:4943–4954CrossRefPubMedPubMedCentral

35.

Lee CM, Yang P, Chen LC, Chen CC, Wu SC, Cheng HY, Chang YS (2011) A novel role of RASSF9 in maintaining epidermal homeostasis. PLoS ONE 6:e17867CrossRefPubMedPubMedCentral

36.

Cohen-Salmon M, El-Amraoui A, Leibovici M, Petit C (1997) Otogelin: a glycoprotein specific to the acellular membranes of the inner ear. Proc Natl Acad Sci USA 94:14450–14455CrossRefPubMedPubMedCentral

37.

Simmler MC, Cohen-Salmon M, El-Amraoui A, Guillaud L, Benichou JC, Petit C, Panthier JJ (2000) Targeted disruption of otog results in deafness and severe imbalance. Nat Genet 24:139–143CrossRefPubMed

38.

Schraders M, Ruiz-Palmero L, Kalay E, Oostrik J, del Castillo FJ, Sezgin O, Beynon AJ, Strom TM, Pennings RJ, Zazo Seco C, Oonk AM, Kunst HP, Domínguez-Ruiz M, García-Arumi AM, del Campo M, Villamar M, Hoefsloot LH, Moreno F, Admiraal RJ, del Castillo I, Kremer H (2012) Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment. Am J Hum Genet 91:883–889CrossRefPubMedPubMedCentral

Title: Candidate susceptibility variants in angioimmunoblastic T-cell lymphoma
Authors: Iikki Donner
Riku Katainen
Eevi Kaasinen
Mervi Aavikko
Lauri J. Sipilä
Eero Pukkala
Lauri A. Aaltonen
Publication date: 01-01-2019
Publisher: Springer Netherlands
Published in: Familial Cancer / Issue 1/2019
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-018-0099-x

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