The role of ALK in human neoplasia

The role of ALK in human neoplasia

George Karagkounis, Christos Masaoutis, Theodore Argyrakos, Dimitra Rontogianni, George Stranjalis, Damianos Sakas, Dina Tiniakos

Abstract


ALK (Anaplastic Lymphoma Kinase) protein belongs to the receptor tyrosine kinase (RTK) family and is normally involved in multiple signaling pathways regulating various cellular functions. Since the first report of a chromosomal translocation involving an alk locus in anaplastic large cell lymphoma (ALCL), ALK has been studied in many other human neoplasms. Multiple alterations of the alk gene have been discovered, such as point mutations, multiple gene copies (neuroblastoma), translocations (TPM-ALK positive inflammatory myofibroblastic tumors, IMTs) and inversions [EML4-ALK positive non-small cell lung carcinomas (NSCLC)]. The fusion proteins formed from gene translocations can lead to activation and up-regulation of ALK-related signaling pathways, resulting in uncontrolled cell proliferation and neoplastic growth. RTKs such as ALK have become attractive targets for the development of targeted therapies. RTK inhibitors of the 1st (such as Crizotinib) and 2nd  generation are already in use in selected NSCLC, IMT and ALCL cases, and one of the goals in modern oncology is to expand their application for the treatment of many other neoplasms in the near future. In this review, we present data on the alk gene, protein and ligands, molecular pathways it relates to, and pathological expression in ALK-related malignancies.


Keywords


ALK, cancer, carcinoma, neoplasia, receptor tyrosine kinases, inversion, translocation, signaling pathway, proliferation, prognosis

Full Text:

Read article as PDF

References


ALK ALK receptor tyrosine kinase [Homo sapiens (human)] - Gene - NCBI. http://www.ncbi.nlm.nih.gov/gene/238. Accessed January 14, 2019.

Yazdi MH, Faramarzi MA, Nikfar S, Abdollahi M. A Comprehensive Review of Clinical Trials on EGFR Inhibitors Such as Cetuximab and Panitumumab as Monotherapy and in Combination for Treatment of Metastatic Colorectal Cancer. Avicenna J Med Biotechnol. 2015;7(4):134-144.

Zanardi E, Bregni G, de Braud F, Di Cosimo S. Better Together: Targeted Combination Therapies in Breast Cancer. Semin Oncol. 2015;42(6):887-895.

Firwana B, Sonbol MB, Diab M, Raza S, Hasan R, Yousef I, Zarzour A, Garipalli A, Doll D, Murad MH, Al-Kali A. Tyrosine kinase inhibitors as a first-line treatment in patients with newly diagnosed chronic myeloid leukemia in chronic phase: A mixed-treatment comparison. Int J Cancer. 2016;138(6):1545-1553.

Jang S, Atkins MB. Which drug, and when, for patients with BRAF-mutant melanoma? Lancet Oncol. 2013;14(2):e60-e69.

Kwak EL, Bang Y-J, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou S-HI, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim W-H, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693-1703.

Butrynski JE, D’Adamo DR, Hornick JL, Dal Cin P, Antonescu CR, Jhanwar SC, Ladanyi M, Capelletti M, Rodig SJ, Ramaiya N, Kwak EL, Clark JW, Wilner KD, Christensen JG, Jänne PA, Maki RG, Demetri GD, Shapiro GI. Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med. 2010;363(18):1727-1733.

Gambacorti Passerini C, Farina F, Stasia A, Redaelli S, Ceccon M, Mologni L, Messa C, Guerra L, Giudici G, Sala E, Mussolin L, Deeren D, King MH, Steurer M, Ordemann R, Cohen AM, Grube M, Bernard L, Chiriano G, Antolini L, Piazza R. Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients. J Natl Cancer Inst. 2014;106(2):djt378.

Morris SW, Kirstein MN, Valentine MB, Dittmer K, Shapiro DN, Look AT, Saltman DL. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1995;267(5196):316-317.

Iwahara T, Fujimoto J, Wen D, Cupples R, Bucay N, Arakawa T, Mori S, Ratzkin B, Yamamoto T. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene. 1997;14(4):439-449.

ALK ALK receptor tyrosine kinase [Homo sapiens (human)] - Gene - NCBI. http://www.ncbi.nlm.nih.gov/gene/238. Accessed January 14, 2019.

Palmer RH, Vernersson E, Grabbe C, Hallberg B. Anaplastic lymphoma kinase: signalling in development and disease. Biochem J. 2009;420(3):345-361.

Website. http://www.nordiqc.org/Run-39-B16-H4/Assessment/Run39_ALK.pdf. Accessed January 14, 2019.

Polgar D, Leisser C, Maier S, Strasser S, Rüger B, Dettke M, Khorchide M, Simonitsch I, Cerni C, Krupitza G. Truncated ALK derived from chromosomal translocation t(2;5)(p23;q35) binds to the SH3 domain of p85-PI3K. Mutat Res/Fundam Mol Mech Mutag. 2005;570(1):9-15.

Muramatsu H, Zou K, Sakaguchi N, Ikematsu S, Sakuma S, Muramatsu T. LDL receptor-related protein as a component of the midkine receptor. Biochem Biophys Res Commun. 2000;270(3):936-941.

Muramatsu H, Zou P, Suzuki H, Oda Y, Chen G-Y, Sakaguchi N, Sakuma S, Maeda N, Noda M, Takada Y, Muramatsu T. alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine, a heparin-binding growth factor. J Cell Sci. 2004;117(Pt 22):5405-5415.

Lu KV, Jong KA, Kim GY, Singh J, Dia EQ, Yoshimoto K, Wang MY, Cloughesy TF, Nelson SF, Mischel PS. Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. J Biol Chem. 2005;280(29):26953-26964.

Bowden ET, Stoica GE, Wellstein A. Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase. J Biol Chem. 2002;277(39):35862-35868.

Kuo AH, Stoica GE, Riegel AT, Wellstein A. Recruitment of insulin receptor substrate-1 and activation of NF-kappaB essential for midkine growth signaling through anaplastic lymphoma kinase. Oncogene. 2007;26(6):859-869.

Reshetnyak AV, Mohanty J, Tomé F, Puleo DE, Plotnikov AN, Ahmed M, Kaur N, Poliakov A, Cinnaiyan AM, Lax I, Schlessinger J. Identification of a biologically active fragment of ALK and LTK-Ligand 2 (augmentor-α). Proc Natl Acad Sci U S A. 2018;115(33):8340-8345.

Fadeev A, Mendoza-Garcia P, Irion U, Guan J, Pfeifer K, Wiessner S, Serluca F, Singh AP, Nüsslein-Volhard C, Palmer RH. ALKALs are in vivo ligands for ALK family receptor tyrosine kinases in the neural crest and derived cells. Proc Natl Acad Sci U S A. 2018;115(4):E630-E638.

Mi R, Chen W, Höke A. Pleiotrophin is a neurotrophic factor for spinal motor neurons. Proc Natl Acad Sci U S A. 2007;104(11):4664-4669.

Li R, Morris SW. Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy. Med Res Rev. 2008;28(3):372-412.

https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed January 30, 2019.

Kim H, Yoo S-B, Choe J-Y, Paik JH, Xu X, Nitta H, Zhang W, Grogan TM, Lee C-T, Jheon S, Chung J-H. Detection of ALK Gene Rearrangement in Non-small Cell Lung Cancer: A Comparison of Fluorescence In Situ Hybridization and Chromogenic In Situ Hybridization with Correlation of ALK Protein Expression. J Thorac Oncol. 2011;6(8):1359-1366.

Hofman P. ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients. Cancers . 2017;9(8). doi:10.3390/cancers9080106.

Campo E, Harris NL, Pileri SA, Jaffe ES, Stein H, Thiele J. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer; 2017.

Palacios G, Shaw TI, Li Y, Singh RK, Valentine M, Sandlund JT, Lim MS, Mullighan CG, Leventaki V. Novel ALK fusion in anaplastic large cell lymphoma involving EEF1G, a subunit of the eukaryotic elongation factor-1 complex. Leukemia. 2017;31(3):743-747.

Fukuhara S, Nomoto J, Kim S-W, Taniguchi H, Miyagi Maeshima A, Tobinai K, Kobayashi Y. Partial deletion of the ALK gene in ALK-positive anaplastic large cell lymphoma. Hematol Oncol. 2018;36(1):150-158.

Murga-Zamalloa CA, Mendoza-Reinoso V, Sahasrabuddhe AA, Rolland D, Hwang SR, McDonnell SRP, Sciallis AP, Wilcox RA, Bashur V, Elenitoba-Johnson K, Lim MS. NPM-ALK phosphorylates WASp Y102 and contributes to oncogenesis of anaplastic large cell lymphoma. Oncogene. 2017;36(15):2085-2094.

Pomari E, Basso G, Bresolin S, Pillon M, Carraro E, d’Amore ES, Viola G, Frasson C, Basso K, Bonvini P, Mussolin L. NPM-ALK expression levels identify two distinct subtypes of paediatric anaplastic large cell lymphoma. Leukemia. 2017;31(2):498-501.

Hu L, Zhang X, Wang J, Wang S, Amin HM, Shi P. Involvement of oncogenic tyrosine kinase NPM-ALK in trifluoperazine-induced cell cycle arrest and apoptosis in ALK + anaplastic large cell lymphoma. Hematology. 2018;23(5):284-290.

Huang H, Gheorghe G, North PE, Suchi M. Expanding the Phenotype of ALK-positive Histiocytosis: A Report of 2 Cases. Pediatr Dev Pathol. 2018;21(5):449-455.

Toll AD, Maleki Z. Cytomorphology of non-small cell lung carcinoma with anaplastic lymphoma kinase gene rearrangement. Diagn Cytopathol. 2015;43(1):8-15.

Skov BG, Clementsen P, Larsen KR, Sørensen JB, Mellemgaard A. The prevalence of ALK rearrangement in pulmonary adenocarcinomas in an unselected Caucasian population from a defined catchment area: impact of smoking. Histopathology. 2017;70(6):889-895.

Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S-I, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561-566.

Du X, Shao Y, Qin H-F, Tai Y-H, Gao H-J. ALK-rearrangement in non-small-cell lung cancer (NSCLC). Thorac Cancer. 2018;9(4):423-430.

Watanabe J, Togo S, Sumiyoshi I, Namba Y, Suina K, Mizuno T,

Kadoya K, Motomura H, Iwai M, Nagaoka T, Sasaki S, Hayashi T, Uekusa T, Abe K, Urata Y, Sakurai F, Mizuguchi H, Kato S, Takahashi K. Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review. Oncotarget. 2018;9(35):24000-24013.

Hayashi N, Fujita A, Saikai T, Takabatake H, Sotoshiro M, Sekine K, Kawana A. Large Cell Neuroendocrine Carcinoma Harboring an Anaplastic Lymphoma Kinase (ALK) Rearrangement with Response to Alectinib. Intern Med. 2018;57(5):713-716.

Nakajima M, Uchiyama N, Shigemasa R, Matsumura T, Matsuoka R, Nomura A. Atypical Carcinoid Tumor with Anaplastic Lymphoma Kinase (ALK) Rearrangement Successfully Treated by an ALK Inhibitor. Intern Med. 2016;55(21):3151-3153.

Taguchi R, Higuchi K, Sudo M, Misawa K, Miyamoto T, Mishima O, Kitano M, Azuhata K, Ito N. A case of anaplastic lymphoma kinase (ALK)-positive ciliated muconodular papillary tumor (CMPT) of the lung. Pathol Int. 2017;67(2):99-104.

Jin Y, Shen X, Shen L, Sun Y, Chen H, Li Y. Ciliated muconodular papillary tumor of the lung harboring ALK gene rearrangement: Case report and review of the literature. Pathol Int. 2017;67(3):171-175.

Lococo F, Bisagni A, Mengoli MC, Cavazza A, Rossi G. ALK Rearrangement Detected in a Focus of Pulmonary Atypical Adenomatous Hyperplasia. J Thorac Oncol. 2017;12(5):e37-e39.

Martín Martorell P, Huerta M, Compañ Quilis A, Abellán R, Seda E, Blesa S, Chaves FJ, Dualde Beltrán D, Roselló Keränen S, Franco J, Insa A. Coexistence of EGFR, KRAS, BRAF, and PIK3CA Mutations and ALK Rearrangement in a Comprehensive Cohort of 326 Consecutive Spanish Nonsquamous NSCLC Patients. Clin Lung Cancer. 2017;18(6):e395-e402.

Wang Z, Yang H, Luo S, Liu B, Zhang N, Li L, Zhou S, Shen R, Xie X. Anaplastic lymphoma kinase gene rearrangement predicts better prognosis in NSCLC patients: A meta-analysis. Lung Cancer. 2017;112:1-9.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-Small Cell Lung Cancer (Version 3.2019 - January 18, 2019). January 2019. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed January 30, 2019.

Patel M, Malhotra J, Jabbour SK. Examining EML4-ALK variants in the clinical setting: the next frontier? J Thorac Dis. 2018;10(Suppl 33):S4104-S4107.

Spagnuolo A, Maione P, Gridelli C. Evolution in the treatment landscape of non-small cell lung cancer with ALK gene alterations: from the first- to third-generation of ALK inhibitors. Expert Opin Emerg Drugs. 2018;23(3):231-241.

Yun MR, Lim SM, Kim S-K, Choi HM, Pyo K-H, Kim SK, Lee JM, Lee YW, Choi JW, Kim HR, Hong MH, Haam K, Huh N, Kim J-H, Kim YS, Shim HS, Soo RA, Shih J-Y, Yang JC-H, Kim M, Cho BC. Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors. Cancer Res. 2018;78(12):3350-3362.

Shanshal M, Awasthi S. MINI01.05: RALPB1 Mediate ALK Resistance in Non-Small Cell Lung Cancer: Topic: Medical Oncology. J Thorac Oncol. 2016;11(11S):S258-S259.

Dardaei L, Wang HQ, Singh M, Fordjour P, Shaw KX, Yoda S, Kerr G, Yu K, Liang J, Cao Y, Chen Y, Lawrence MS, Langenbucher A, Gainor JF, Friboulet L, Dagogo-Jack I, Myers DT, Labrot E, Ruddy D, Parks M, Lee D, DiCecca RH, Moody S, Hao H, Mohseni M, LaMarche M, Williams J, Hoffmaster K, Caponigro G, Shaw AT, Hata AN, Benes CH, Li F, Engelman JA. SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors. Nat Med. 2018;24(4):512-517.

Perez-Pinera P, Chang Y, Astudillo A, Mortimer J, Deuel TF. Anaplastic lymphoma kinase is expressed in different subtypes of human breast cancer. Biochem Biophys Res Commun. 2007;358(2):399-403.

Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, Chen H, Omeroglu G, Meterissian S, Omeroglu A, Hallett M, Park M. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008;14(5):518-527.

Lin E, Li L, Guan Y, Soriano R, Rivers CS, Mohan S, Pandita A, Tang J, Modrusan Z. Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers. Mol Cancer Res. 2009;7(9):1466-1476.

Perez-Pinera P, Zhang W, Chang Y, Vega JA, Deuel TF. Anaplastic lymphoma kinase is activated through the pleiotrophin/receptor protein-tyrosine phosphatase beta/zeta signaling pathway: an alternative mechanism of receptor tyrosine kinase activation. J Biol Chem. 2007;282(39):28683-28690.

Siraj AK, Beg S, Jehan Z, Prabhakaran S, Ahmed M, R Hussain A, Al-Dayel F, Tulbah A, Ajarim D, Al-Kuraya KS. ALK alteration is a frequent event in aggressive breast cancers. Breast Cancer Res. 2015;17:127.

Schoppmann SF, Streubel B, Birner P. Amplification but not translocation of anaplastic lymphoma kinase is a frequent event in oesophageal cancer. Eur J Cancer. 2013;49(8):1876-1881.

Bavi P, Jehan Z, Bu R, Prabhakaran S, Al-Sanea N, Al-Dayel F, Al-Assiri M, Al-Halouly T, Sairafi R, Uddin S, Al-Kuraya KS. ALK gene amplification is associated with poor prognosis in colorectal carcinoma. Br J Cancer. 2013;109(10):2735-2743.

Houang M, Toon CW, Clarkson A, Sioson L, de Silva K, Watson N, Singh NR, Chou A, Gill AJ. ALK and ROS1 overexpression is very rare in colorectal adenocarcinoma. Appl Immunohistochem Mol Morphol. 2015;23(2):134-138.

Pietrantonio F, Di Nicolantonio F, Schrock AB, Lee J, Tejpar S, Sartore-Bianchi A, Hechtman JF, Christiansen J, Novara L, Tebbutt N, Fucà G, Antoniotti C, Kim ST, Murphy D, Berenato R, Morano F, Sun J, Min B, Stephens PJ, Chen M, Lazzari L, Miller VA, Shoemaker R, Amatu A, Milione M, Ross JS, Siena S, Bardelli A, Ali SM, Falcone A, de Braud F, Cremolini C. ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer. J Natl Cancer Inst. 2017;109(12). doi:10.1093/jnci/djx089.

Jia S-W, Fu S, Wang F, Shao Q, Huang H-B, Shao J-Y. ALK gene copy number gain and its clinical significance in hepatocellular carcinoma. World J Gastroenterol. 2014;20(1):183-192.

Liu J, Jin H, Tian H, Lian G, Chen S, Li J, Zhang X, Ma D. Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma. Oncol Lett. 2016;11(1):213-223.

Ormanns S, Assmann G, Reu S, Gallmeier E, Bader DC, Kleespies A, Haas M, Kruger S, Heinemann V, Kirchner T, Boeck S. ALK expression is absent in pancreatic ductal adenocarcinoma. J Cancer Res Clin Oncol. 2014;140(9):1625-1628.

Graham RPD, Oliveira AM, Zhang L. Rare ALK expression but no ALK rearrangement in pancreatic ductal adenocarcinoma and neuroendocrine tumors. Pancreas. 2013;42(6):949-951.

Singhi AD, Ali SM, Lacy J, Hendifar A, Nguyen K, Koo J, Chung JH, Greenbowe J, Ross JS, Nikiforova MN, Zeh HJ, Sarkaria IS, Dasyam A, Bahary N. Identification of Targetable Rearrangements in Pancreatic Ductal Adenocarcinoma. J Natl Compr Canc Netw. 2017;15(5):555-562.

Smith NE, Deyrup AT, Mariño-Enriquez A, Fletcher JA, Bridge JA, Illei PB, Netto GJ, Argani P. VCL-ALK renal cell carcinoma in children with sickle-cell trait: the eighth sickle-cell nephropathy? Am J Surg Pathol. 2014;38(6):858-863.

Bodokh Y, Ambrosetti D, Kubiniek V, Tibi B, Durand M, Amiel J, Pertuit M, Barlier A, Pedeutour F. ALK-TPM3 rearrangement in adult renal cell carcinoma: Report of a new case showing loss of chromosome 3 and literature review. Cancer Genet. 2018;221:31-37.

Yu W, Wang Y, Jiang Y, Zhang W, Li Y. Genetic analysis and clinicopathological features of ALK -rearranged renal cell carcinoma in a large series of resected Chinese renal cell carcinoma patients and literature review. Histopathology. 2017;71(1):53-62.

Sugawara E, Togashi Y, Kuroda N, Sakata S, Hatano S, Asaka R, Yuasa T, Yonese J, Kitagawa M, Mano H, Ishikawa Y, Takeuchi K. Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method. Cancer. 2012;118(18):4427-4436.

Cajaiba MM, Jennings LJ, George D, Perlman EJ. Expanding the spectrum of ALK-rearranged renal cell carcinomas in children: Identification of a novel HOOK1-ALK fusion transcript. Genes Chromosomes Cancer. 2016;55(10):814-817.

Kusano H, Togashi Y, Akiba J, Moriya F, Baba K, Matsuzaki N, Yuba Y, Shiraishi Y, Kanamaru H, Kuroda N, Sakata S, Takeuchi K, Yano H. Two Cases of Renal Cell Carcinoma Harboring a Novel STRN-ALK Fusion Gene. Am J Surg Pathol. 2016;40(6):761-769.

Hodge JC, Pearce KE, Sukov WR. Distinct ALK-rearranged and VCL-negative papillary renal cell carcinoma variant in two adults without sickle cell trait. Mod Pathol. 2013;26(4):604-605.

Lee C, Park JW, Suh JH, Nam KH, Moon KC. ALK-Positive Renal Cell Carcinoma in a Large Series of Consecutively Resected Korean Renal Cell Carcinoma Patients. Korean J Pathol. 2013;47(5):452.

Jeanneau M, Gregoire V, Desplechain C, Escande F, Tica DP, Aubert S, Leroy X. ALK rearrangements-associated renal cell carcinoma (RCC) with unique pathological features in an adult. Pathol Res Pract. 2016;212(11):1064-1066.

Chou A, Fraser S, Toon CW, Clarkson A, Sioson L, Farzin M, Cussigh C, Aniss A, O’Neill C, Watson N, Clifton-Bligh RJ, Learoyd DL, Robinson BG, Selinger CI, Delbridge LW, Sidhu SB, O’Toole SA, Sywak M, Gill AJ. A detailed clinicopathologic study of ALK-translocated papillary thyroid carcinoma. Am J Surg Pathol. 2015;39(5):652-659.

Arndt A, Steinestel K, Rump A, Sroya M, Bogdanova T, Kovgan L, Port M, Abend M, Eder S. Anaplastic lymphoma kinase ( ALK ) gene rearrangements in radiation-related human papillary thyroid carcinoma after the Chernobyl accident : ALK rearrangements in post-Chernobyl PTC samples. Hip Int. 2018;4(3):175-183.

Murugan AK, Xing M. Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene. Cancer Res. 2011;71(13):4403-4411.

Pérot G, Soubeyran I, Ribeiro A, Bonhomme B, Savagner F, Boutet-Bouzamondo N, Hostein I, Bonichon F, Godbert Y, Chibon F. Identification of a recurrent STRN/ALK fusion in thyroid carcinomas. PLoS One. 2014;9(1):e87170.

Bastos AU, de Jesus AC, Cerutti JM. and kinase fusions are recurrent events in papillary thyroid cancer of adult population. Eur J Endocrinol. 2018;178(1):85-93.

Ji JH, Oh YL, Hong M, Yun JW, Lee H-W, Kim D, Ji Y, Kim D-H, Park W-Y, Shin H-T, Kim K-M, Ahn M-J, Park K, Sun J-M. Identification of Driving ALK Fusion Genes and Genomic Landscape of Medullary Thyroid Cancer. PLoS Genet. 2015;11(8):e1005467.

Veija T, Koljonen V, Bohling T, Kero M, Knuutila S, Sarhadi VK. Aberrant expression of ALK and EZH2 in Merkel cell carcinoma. BMC Cancer. 2017;17(1):236.

Filtenborg-Barnkob BE, Bzorek M. Expression of anaplastic lymphoma kinase in Merkel cell carcinomas. Hum Pathol. 2013;44(8):1656-1664.

Tang S, Yang F, Du X, Lu Y, Zhang L, Zhou X. Aberrant Expression of Anaplastic Lymphoma Kinase in Ovarian Carcinoma Independent of Gene Rearrangement. Int J Gynecol Pathol. 2016;35(4):337-347.

Craig JW, Quade BJ, Muto MG, MacConaill LE. Endometrial cancer with an rearrangement. Cold Spring Harb Mol Case Stud. 2018;4(4). doi:10.1101/mcs.a003020.

Mönch D, Bode-Erdmann S, Kalla J, Sträter J, Schwänen C, Falkenstern-Ge R, Klumpp S, Friedel G, Ott G, Kalla C. A subgroup of pleural mesothelioma expresses ALK protein and may be targetable by combined rapamycin and crizotinib therapy. Oncotarget. 2018;9(29):20781-20794.

Hung YP, Dong F, Watkins JC, Nardi V, Bueno R, Dal Cin P, Godleski JJ, Crum CP, Chirieac LR. Identification of ALK Rearrangements in Malignant Peritoneal Mesothelioma. JAMA Oncol. 2018;4(2):235-238.

Cessna MH, Zhou H, Sanger WG, Perkins SL, Tripp S, Pickering D, Daines C, Coffin CM. Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases. Mod Pathol. 2002;15(9):931-938.

Coffin CM, Watterson J, Priest JR, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol. 1995;19(8):859-872.

Chun YS, Wang L, Nascimento AG, Moir CR, Rodeberg DA. Pediatric inflammatory myofibroblastic tumor: anaplastic lymphoma kinase (ALK) expression and prognosis. Pediatr Blood Cancer. 2005;45(6):796-801.

Kimbara S, Takeda K, Fukushima H, Inoue T, Okada H, Shibata Y, Katsushima U, Tsuya A, Tokunaga S, Daga H, Okuno T, Inoue T. A case report of epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK fusion gene treated with the ALK inhibitor, crizotinib. Jpn J Clin Oncol. 2014;44(9):868-871.

Lee J-C, Li C-F, Huang H-Y, Zhu M-J, Mariño-Enríquez A, Lee C-T, Ou W-B, Hornick JL, Fletcher JA. ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma. J Pathol. 2017;241(3):316-323.

Jiang Q, Tong H-X, Hou Y-Y, Zhang Y, Li J-L, Zhou Y-H, Xu J, Wang J-Y, Lu W-Q. Identification of EML4-ALK as an alternative fusion gene in epithelioid inflammatory myofibroblastic sarcoma. Orphanet J Rare Dis. 2017;12(1):97.

Devereaux KA, Kunder CA, Longacre TA. ALK-rearranged Tumors Are Highly Enriched in the STUMP Subcategory of Uterine Tumors. Am J Surg Pathol. 2019;43(1):64-74.

Mohammad N, Haimes JD, Mishkin S, Kudlow BA, Leong MY, Chew SH, Koay E, Whitehouse A, Cope N, Ali RH, Köbel M, Stewart CJR, McCluggage WG, Lee C-H. ALK Is a Specific Diagnostic Marker for Inflammatory Myofibroblastic Tumor of the Uterus. Am J Surg Pathol. 2018;42(10):1353-1359.

Dickson BC, Swanson D, Charames GS, Fletcher CD, Hornick JL. Epithelioid fibrous histiocytoma: molecular characterization of ALK fusion partners in 23 cases. Mod Pathol. 2018;31(5):753-762.

Perret RE, Jullie M-L, Vergier B, Coindre J-M, Le Loarer F. A subset of so-called dermal non-neural granular cell tumours are underlined by ALK fusions, further supporting the idea that they represent a variant of epithelioid fibrous histiocytoma. Histopathology. 2018;73(3):532-534.

Cheah AL, Zou Y, Lanigan C, Billings SD, Rubin BP, Hornick JL, Goldblum JR. ALK Expression in Angiomatoid Fibrous Histiocytoma: A Potential Diagnostic Pitfall. Am J Surg Pathol. 2019;43(1):93-101.

Szablewski V, Laurent-Roussel S, Rethers L, Rommel A, Van Eeckhout P, Camboni A, Willocz P, Copie-Bergman C, Ortonne N. Atypical fibrous histiocytoma of the skin with CD30 and p80/ALK1 positivity and ALK gene rearrangement. J Cutan Pathol. 2014;41(9):715-719.

Fleuren EDG, Vlenterie M, van der Graaf WTA, Hillebrandt-Roeffen MHS, Blackburn J, Ma X, Chan H, Magias MC, van Erp A, van Houdt L, Cebeci SAS, van de Ven A, Flucke UE, Heyer EE, Thomas DM, Lord CJ, Marini KD, Vaghjiani V, Mercer TR, Cain JE, Wu J, Versleijen-Jonkers YMH, Daly RJ. Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes. Cancer Res. 2017;77(16):4279-4292.

Stoica GE, Kuo A, Powers C, Bowden ET, Sale EB, Riegel AT, Wellstein A. Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types. J Biol Chem. 2002;277(39):35990-35998.

Grzelinski M, Steinberg F, Martens T, Czubayko F, Lamszus K, Aigner A. Enhanced antitumorigenic effects in glioblastoma on double targeting of pleiotrophin and its receptor ALK. Neoplasia. 2009;11(2):145-156.

Powers C, Aigner A, Stoica GE, McDonnell K, Wellstein A. Pleiotrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth. J Biol Chem. 2002;277(16):14153-14158.

Karagkounis G, Stranjalis G, Argyrakos T, Pantelaion V, Mastoris K, Rontogianni D, Komaitis S, Kalamatianos T, Sakas D, Tiniakos D. Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome. J Clin Pathol. 2017;70(7):593-599.

Chiba R, Akiya M, Hashimura M, Oguri Y, Inukai M, Hara A, Saegusa M. ALK signaling cascade confers multiple advantages to glioblastoma cells through neovascularization and cell proliferation. PLoS One. 2017;12(8):e0183516.

Olsen TK, Panagopoulos I, Meling TR, Micci F, Gorunova L, Thorsen J, Due-Tønnessen B, Scheie D, Lund-Iversen M, Krossnes B, Saxhaug C, Heim S, Brandal P. Fusion genes with ALK as recurrent partner in ependymoma-like gliomas: a new brain tumor entity? Neuro Oncol. 2015;17(10):1365-1373.

Aghajan Y, Levy ML, Malicki DM, Crawford JR. Novel PPP1CB-ALK fusion protein in a high-grade glioma of infancy. BMJ Case Rep. 2016;2016. doi:10.1136/bcr-2016-217189.

Johnson A, Severson E, Gay L, Vergilio J-A, Elvin J, Suh J, Daniel S, Covert M, Frampton GM, Hsu S, Lesser GJ, Stogner-Underwood K, Mott RT, Rush SZ, Stanke JJ, Dahiya S, Sun J, Reddy P, Chalmers ZR, Erlich R, Chudnovsky Y, Fabrizio D, Schrock AB, Ali S, Miller V, Stephens PJ, Ross J, Crawford JR, Ramkissoon SH. Comprehensive Genomic Profiling of 282 Pediatric Low- and High-Grade Gliomas Reveals Genomic Drivers, Tumor Mutational Burden, and Hypermutation Signatures. Oncologist. 2017;22(12):1478-1490.

Saraggi D, Salmaso R, Zamuner C, Munari G, Lanza C, Alaibac MS, Bassetto F, Rugge M, Montesco MC, Cerroni L, Fassan M. Prevalence of ALK gene alterations among the spectrum of plexiform spitzoid lesions. J Am Acad Dermatol. 2018;79(4):728-735.

Farah M, Nagarajan P, Curry JL, Tang Z, Kim T-B, Aung PP, Torres-Cabala CA, Eterovic AK, Wargo JA, Prieto VG, Tetzlaff MT. Spitzoid melanoma with histopathological features of ALK gene rearrangement exhibiting ALK copy number gain: a novel mechanism of ALK activation in spitzoid neoplasia. Br J Dermatol. June 2018. doi:10.1111/bjd.16881.

Fujimoto M, Togashi Y, Matsuzaki I, Baba S, Takeuchi K, Inaba Y, Jinnin M, Murata S-I. A case report of atypical Spitz tumor harboring a novel MLPH-ALK gene fusion with discordant ALK immunohistochemistry results. Hum Pathol. 2018;80:99-103.

Rand AJ, Flejter WL, Dowling CA, Brooke LM, Boland GM, Kroshinsky D, Rosenblum IR, Hernandez-Perez M, Reimann JDR. Atypical ALK-positive Spitz tumors with 9p21 homozygous deletion: Report of two cases and review of the literature. J Cutan Pathol. 2018;45(2):136-140.

Perron E, Pissaloux D, Charon Barra C, Karanian M, Lamant L, Parfait S, Alberti L, de la Fouchardière A. Melanocytic Myxoid Spindle Cell Tumor With ALK Rearrangement (MMySTAR): Report of 4 Cases of a Nevus Variant With Potential Diagnostic Challenge. Am J Surg Pathol. 2018;42(5):595-603.

Dunn ALJ, Gardner JM, Kaley JR, Bellamy W, Shalin SC. ALK Rearrangements Are Infrequent in Cellular Blue Nevus and Deep Penetrating Nevus. Am J Dermatopathol. 2018;40(7):469-478.

Niu H-T, Zhou Q-M, Wang F, Shao Q, Guan Y-X, Wen X-Z, Chen L-Z, Feng Q-S, Li W, Zeng Y-X, Zhang X-S. Identification of anaplastic lymphoma kinase break points and oncogenic mutation profiles in acral/mucosal melanomas. Pigment Cell Melanoma Res. 2013;26(5):646-653.

Busam KJ, Vilain RE, Lum T, Busam JA, Hollmann TJ, Saw RPM, Coit DC, Scolyer RA, Wiesner T. Primary and Metastatic Cutaneous Melanomas Express ALK Through Alternative Transcriptional Initiation. Am J Surg Pathol. 2016;40(6):786-795.

Trigg RM, Turner SD. ALK in Neuroblastoma: Biological and Therapeutic Implications. Cancers . 2018;10(4). doi:10.3390/cancers10040113.

Lu F, Kishida S, Mu P, Huang P, Cao D, Tsubota S, Kadomatsu K. NeuroD1 promotes neuroblastoma cell growth by inducing the expression of ALK. Cancer Sci. 2015;106(4):390-396.

De Mariano M, Stigliani S, Moretti S, Parodi F, Croce M, Bernardi C, Pagano A, Tonini GP, Ferrini S, Longo L. A genome-wide microRNA profiling indicates miR-424-5p and miR-503-5p as regulators of ALK expression in neuroblastoma. Oncotarget. 2017;8(34):56518-56532.

Coco S, De Mariano M, Valdora F, Servidei T, Ridola V, Andolfo I, Oberthuer A, Tonini GP, Longo L. Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma. J Hum Genet. 2012;57(10):682-684.

Łastowska M, Trubicka J, Niemira M, Paczkowska-Abdulsalam M, Karkucińska-Więckowska A, Kaleta M, Drogosiewicz M, Tarasińska M, Perek-Polnik M, Krętowski A, Dembowska-Bagińska B, Grajkowska W, Pronicki M, Matyja E. ALK Expression Is a Novel Marker for the WNT-activated Type of Pediatric Medulloblastoma and an Indicator of Good Prognosis for Patients. Am J Surg Pathol. 2017;41(6):781-787.

van Gaal JC, Flucke UE, Roeffen MHS, de Bont ESJM, Sleijfer S, Mavinkurve-Groothuis AMC, Suurmeijer AJH, van der Graaf WTA, Versleijen-Jonkers YMH. Anaplastic lymphoma kinase aberrations in rhabdomyosarcoma: clinical and prognostic implications. J Clin Oncol. 2012;30(3):308-315.

Yoshida A, Shibata T, Wakai S, Ushiku T, Tsuta K, Fukayama M, Makimoto A, Furuta K, Tsuda H. Anaplastic lymphoma kinase status in rhabdomyosarcomas. Mod Pathol. 2013;26(6):772-781.

Pulford K, Lamant L, Morris SW, Butler LH, Wood KM, Stroud D, Delsol G, Mason DY. Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood. 1997;89(4):1394-1404.

Onciu M, Behm FG, Downing JR, Shurtleff SA, Raimondi SC, Ma Z, Morris SW, Kennedy W, Jones SC, Sandlund JT. ALK-positive plasmablastic B-cell lymphoma with expression of the NPM-ALK fusion transcript: report of 2 cases. Blood. 2003;102(7):2642-2644.

Reichard KK, McKenna RW, Kroft SH. ALK-positive diffuse large B-cell lymphoma: report of four cases and review of the literature. Mod Pathol. 2007;20(3):310-319.

Takeuchi K, Soda M, Togashi Y, Ota Y, Sekiguchi Y, Hatano S, Asaka R, Noguchi M, Mano H. Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma. Haematologica. 2011;96(3):464-467.

Bedwell C, Rowe D, Moulton D, Jones G, Bown N, Bacon CM. Cytogenetically complex SEC31A-ALK fusions are recurrent in ALK-positive large B-cell lymphomas. Haematologica. 2011;96(2):343-346.

Wang W-Y, Gu L, Liu W-P, Li G-D, Liu H-J, Ma Z-G. ALK-positive extramedullary plasmacytoma with expression of the CLTC-ALK fusion transcript. Pathol Res Pract. 2011;207(9):587-591.

Ying J, Lin C, Wu J, Guo L, Qiu T, Ling Y, Shan L, Zhou H, Zhao D, Wang J, Liang J, Zhao J, Jiao Y, Lu N, Zhao H. Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population. PLoS One. 2015;10(12):e0144731.

Lee J, Kim HC, Hong JY, Wang K, Kim SY, Jang J, Kim ST, Park JO, Lim HY, Kang WK, Park YS, Lee J, Lee WY, Park YA, Huh JW, Yun SH, Do I-G, Kim SH, Balasubramanian S, Stephens PJ, Ross JS, Li GG, Hornby Z, Ali SM, Miller VA, Kim K-M, Ou S-HI. Detection of novel and potentially actionable anaplastic lymphoma kinase (ALK) rearrangement in colorectal adenocarcinoma by immunohistochemistry screening. Oncotarget. 2015;6(27):24320-24332.

Carneiro BA, Pamarthy S, Shah AN, Sagar V, Unno K, Han H, Yang XJ, Costa RB, Nagy RJ, Lanman RB, Kuzel TM, Ross JS, Gay L, Elvin JA, Ali SM, Cristofanilli M, Chae YK, Giles FJ, Abdulkadir SA. Anaplastic Lymphoma Kinase Mutation ( F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib. Clin Cancer Res. 2018;24(12):2732-2739.

Bennett JA, Nardi V, Rouzbahman M, Morales-Oyarvide V, Nielsen GP, Oliva E. Inflammatory myofibroblastic tumor of the uterus: a clinicopathological, immunohistochemical, and molecular analysis of 13 cases highlighting their broad morphologic spectrum. Mod Pathol. 2017;30(10):1489-1503.

Takita J. The role of anaplastic lymphoma kinase in pediatric cancers. Cancer Sci. 2017;108(10):1913-1920.

Trubicka J, Szperl M, Grajkowska W, Karkucińska-Więckowska A, Tarasińska M, Falana K, Dembowska-Bagińska B, Łastowska M. Identification of a novel inherited ALK variant M1199L in the WNT type of medulloblastoma. Folia Neuropathol. 2016;54(1):23-30.

Kazakov DV, Kyrpychova L, Martinek P, Grossmann P, Steiner P, Vanecek T, Pavlovsky M, Bencik V, Michal M, Michal M. ALK Gene Fusions in Epithelioid Fibrous Histiocytoma: A Study of 14 Cases, With New Histopathological Findings. Am J Dermatopathol. 2018;40(11):805-814.

Schöffski P, Sufliarsky J, Gelderblom H, Blay J-Y, Strauss SJ, Stacchiotti S, Rutkowski P, Lindner LH, Leahy MG, Italiano A, Isambert N, Debiec-Rychter M, Sciot R, Van Cann T, Marréaud S, Nzokirantevye A, Collette S, Wozniak A. Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial. Lancet Respir Med. 2018;6(6):431-441.

Villalobos VM, Camidge DR. Targeting ALK in inflammatory myofibroblastic tumours. The Lancet Respiratory Medicine. 2018;6(6):405-407.

Pal SK, Bergerot P, Dizman N, Bergerot C, Adashek J, Madison R, Chung JH, Ali SM, Jones JO, Salgia R. Responses to Alectinib in ALK-rearranged Papillary Renal Cell Carcinoma. Eur Urol. 2018;74(1):124-128.

Wierdl M, Tsurkan L, Chi L, Hatfield MJ, Tollemar V, Bradley C, Chen X, Qu C, Potter PM. Targeting ALK in pediatric RMS does not induce antitumor activity in vivo. Cancer Chemother Pharmacol. 2018;82(2):251-263.


Refbacks

  • There are currently no refbacks.


Copyright 2015-2017, Hellenic Society of Pathology
ISSN: 2459-3443