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Two cases of Zellweger spectrum disorder with PEX26 mutations in twins

Two cases of Zellweger spectrum disorder with PEX26 mutations in twins

Authors:
Волынец Г.В.,
Скворцова Т.А.,
Никитин А.В.

Журнал: Доказательная гастроэнтерология. 2025;14(1):118-129.

DOI: 10.17116/dokgastro202514011118

Read: 2656 раз

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Abstract

Zellweger spectrum disorders (ZSD) are a group of rare autosomal recessive diseases caused by peroxisome biogenesis defects. They are characterized by multisystem involvement, including neurological impairments, liver and kidney dysfunction, and developmental anomalies. The disease is driven by mutations in PEX genes, which regulate peroxisome formation and function. This article presents two clinical cases of ZSD in twins with a homozygous PEX26 mutation, a rare phenomenon that expands the known genotype-phenotype correlations.

CLINICAL CASE

Twin boys were followed by a pediatrician from 11 months of age. Both exhibited hypotonia, progressive motor impairment, vision loss, and delayed psychomotor development. One twin had a more severe course with early liver involvement, coagulopathy, and portal hypertension. Genetic analysis identified a previously unreported homozygous c.T347A:p.L116Q mutation in exon 3 of the PEX26 gene (NM_017929), likely associated with neonatal adrenoleukodystrophy, a relatively mild ZSD variant.

CONCLUSION

These cases contribute to the understanding of PEX26-related phenotypic manifestations and highlights the heterogeneity of ZSD. The findings suggest a possible link between residual peroxin activity and a milder disease course. Early diagnosis and multidisciplinary management are crucial for improving prognosis and quality of life in children with Zellweger spectrum disorders.

Keywords

  • Zellweger spectrum disorder
  • peroxisomal diseases
  • PEX26 mutation
  • neonatal adrenoleukodystrophy
  • peroxins

Дата поступления: 25.12.2024

Дата принятия в печать: 21.01.2025

Дата публикации: 27.03.2025

References
  1. Wanders RJ, Waterham HR. Biochemistry of mammalian peroxisomes revisited. Annual Review of Biochemistry. 2006;75:295-332. https://doi.org/10.1146/annurev.biochem.74.082803.133329
  2. Wanders RJA, Baes M, Ribeiro D, Ferdinandusse S, Waterham HR. The physiological functions of human peroxisomes. Physiological Reviews. 2023;103(1):957-1024. https://doi.org/10.1152/physrev.00051.2021
  3. Waterham HR, Ferdinandusse S, Wanders RJ. Human disorders of peroxisome metabolism and biogenesis. Biochimica et Biophysica Acta. 2016;1863(5):922-933. https://doi.org/10.1016/j.bbamcr.2015.11.015
  4. Wanders RJ, van Roermund CW, Schutgens RB, Barth PG, Heymans HS, van den Bosch H, Tager JM. The inborn errors of peroxisomal β-oxidation: a review. Journal of Inherited Metabolic Disease. 1990;13(1):4-36. https://doi.org/10.1007/BF01799330
  5. Zhang W, Narvaez Rivas M, Setchell KDR. Tandem mass spectrometry of serum cholestanoic (C27) acids — Typical concentration ranges and application to the study of peroxisomal biogenesis disorders. Journal of Mass Spectrometry and Advances in the Clinical Lab. 2024;34:34-43. https://doi.org/10.1016/j.jmsacl.2024.10.005
  6. Ferdinandusse S, Denis S, Clayton PT, Graham A, Rees JE, Allen JT, McLean BN, Brown AY, Vreken P, Waterham HR, Wanders RJ. Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Nature Genetics. 2000;24(2):188-191. https://doi.org/10.1038/72861
  7. Setchell KD, Heubi JE, Bove KE, O’Connell NC, Brewsaugh T, Steinberg SJ, Moser A, Squires RH Jr. Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy. Gastroenterology. 2003;124(1):217-232. https://doi.org/10.1053/gast.2003.50017
  8. Verhagen JM, Huijmans JG, Williams M, van Ruyven RL, Bergen AA, Wouters CH, Brooks AS. Incidental finding of alpha-methylacyl-CoA racemase deficiency in a patient with oculocutaneous albinism type 4. American Journal of Medical Genetics. 2012;158A(11):2931-2934. https://doi.org/10.1002/ajmg.a.35611
  9. Smith JJ, Aitchison JD. Peroxisomes take shape. Nature Reviews. Molecular Cell Biology. 2013;14(12):803-817. https://doi.org/10.1038/nrm3700
  10. Watkins PA, Chen L, Braverman N. Peroxisomal disordersin children. In: Suchy FJ, Sokol RJ, Balisreri WF, eds. Liver Disease in Children. 5th ed. Cambridge: Cambridge University Press; 2021: 671-697.
  11. Berendse K, Engelen M, Ferdinandusse S, Majoie CB, Waterham HR, Vaz FM, Koelman JH, Barth PG, Wanders RJ, Poll-The BT. Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood. Journal of Inherited Metabolic Disease. 2016;39(1):93-106. https://doi.org/10.1007/s10545-015-9880-2
  12. Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M. Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Molecular Genetics and Metabolism. 2016;117(3):313-321. https://doi.org/10.1016/j.ymgme.2015.12.009
  13. Di Cara F, Savary S, Kovacs WJ, Kim P, Rachubinski RA. The peroxisome: an up-and-coming organelle in immunometabolism. Trends in Cell Biology. 2023;33(1):70-86. https://doi.org/10.1016/j.tcb.2022.06.001
  14. Lodhi IJ, Wei X, Yin L, Feng C, Adak S, Abou-Ezzi G, Hsu FF, Link DC, Semenkovich CF. Peroxisomal lipid synthesis regulates inflammation by sustaining neutrophil membrane phospholipid composition and viability. Cell Metabolism. 2015;21(1):51-64. https://doi.org/10.1016/j.cmet.2014.12.002
  15. Fletcher JM, Jordan MA, Snelgrove SL, Slattery RM, Dufour FD, Kyparissoudis K, Besra GS, Godfrey DI, Baxter AG. Congenic analysis of the NKT cell control gene Nkt2 implicates the peroxisomal protein Pxmp4. Journal of Immunology. 2008;181(5):3400-3412. https://doi.org/10.4049/jimmunol.181.5.3400
  16. Di Cara F, Sheshachalam A, Braverman NE, Rachubinski RA, Simmonds AJ. Peroxisome-Mediated Metabolism Is Required for Immune Response to Microbial Infection. Immunity. 2017; 47(1):93-106.e7. https://doi.org/10.1016/j.immuni.2017.06.016
  17. Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC. Peroxisomes are signaling platforms for antiviral innate immunity. Cell. 2010;141(4):668-681. https://doi.org/10.1016/j.cell.2010.04.018
  18. Meghnem D, Leong E, Pinelli M, Marshall JS, Di Cara F. Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation. Frontiers in Cell and Developmental Biology. 2022;10:856243. https://doi.org/10.3389/fcell.2022.856243
  19. Nath AS, Parsons BD, Makdissi S, Chilvers RL, Mu Y, Weaver CM, Euodia I, Fitze KA, Long J, Scur M, Mackenzie DP, Makrigiannis AP, Pichaud N, Boudreau LH, Simmonds AJ, Webber CA, Derfalvi B, Hammon Y, Rachubinski RA, Di Cara F. Modulation of the cell membrane lipid milieu by peroxisomal beta-oxidation induces Rho1 signaling to trigger inflammatory responses. Cell Reports. 2022;38(9):110433. https://doi.org/10.1016/j.celrep.2022.110433
  20. Vijayan V, Srinu T, Karnati S, Garikapati V, Linke M, Kamalyan L, Mali SR, Sudan K, Kollas A, Schmid T, Schulz S, Spengler B, Weichhart T, Immenschuh S, Baumgart-Vogt E. A New Immunomodulatory Role for Peroxisomes in Macrophages Activated by the TLR4 Ligand Lipopolysaccharide. Journal of Immunology. 2017;198(6):2414-2425. https://doi.org/10.4049/jimmunol.1601596
  21. Muri J, Corak B, Matsushita M, Baes M, Kopf M. Peroxisomes Are Critical for the Development and Maintenance of B1 and Marginal Zone B Cells but Dispensable for Follicular B Cells and T Cells. Journal of Immunology. 2022;208(4):839-850. https://doi.org/10.4049/jimmunol.2100518
  22. Lucaccioni L, Righi B, Cingolani GM, Lugli L, Della Casa E, Torcetta F, Iughetti L, Berardi A. Overwhelming sepsis in a neonate affected by Zellweger syndrome due to a compound heterozygosis in PEX6 gene: a case report. BMC Medical Genetics. 2020;21(1):229. https://doi.org/10.1186/s12881-020-01175-y
  23. Fazi C, Lodi L, Magi L, Canessa C, Giovannini M, Pelosi C, Pochiero F, Procopio E, Donati MA, Azzari C, Ricci S. Case Report: Zellweger Syndrome and Humoral Immunodeficiency: The Relevance of Newborn Screening for Primary Immunodeficiency. Frontiers in Pediatrics. 2022;10:852943. https://doi.org/10.3389/fped.2022.852943
  24. Al-Sayed M, Al-Hassan S, Rashed M, Qeba M, Coskun S. Preimplantation genetic diagnosis for Zellweger syndrome. Fertility and Sterility. 2007;87(6):1468.e1-1468.e3. https://doi.org/10.1016/j.fertnstert.2006.09.014
  25. Ben Turkia H, Yangui M, Azzouz H, Ben Chehida A, Ben Abelaziz R, Abdelmoula MS, Nasrallah F, Kaabachi N, Wanders R, Tebib N, Ben Dridi MF. A novel mutation in PEX26 gene in Zellweger syndrome: a case report. La Tunisie Medicale. 2011;89(3): 288-291.
  26. Furuki S, Tamura S, Matsumoto N, Miyata N, Moser A, Moser HW, Fujiki Y. Mutations in the peroxin Pex26p responsible for peroxisome biogenesis disorders of complementation group 8 impair its stability, peroxisomal localization, and interaction with the Pex1p x Pex6p complex. Journal of Biological Chemistry. 2006;281(3):1317-1323. https://doi.org/10.1074/jbc.M510044200
  27. He Y, Lin SB, Li WX, Yang L, Zhang R, Chen C, Yuan L. PEX26 gene genotype-phenotype correlation in neonates with Zellweger syndrome. Translational Pediatrics. 2021;10(7):1825-1833. https://doi.org/10.21037/tp-21-103
  28. Matsumoto N, Tamura S, Furuki S, Miyata N, Moser A, Shimozawa N, Moser HW, Suzuki Y, Kondo N, Fujiki Y. Mutations in Novel Peroxin Gene PEX26 That Cause Peroxisome-Biogenesis Disorders of Complementation Group 8 Provide a Genotype-Phenotype Correlation. American Journal of Human Genetics. 2003;73(2):233-246. https://doi.org/10.1086/377004
  29. Rife E, Dunbar AE, Nelson SL, Andersson HC. Stippled Chondral Calcifications of the Patella in Zellweger Syndrome. Journal of Pediatrics. 2018;192:265. https://doi.org/10.1016/j.jpeds.2017.09.064
  30. Steinberg S, Chen L, Wei L, Moser A, Moser H, Cutting G, Braverman N. The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. Molecular Genetics and Metabolism. 2004;83(3):252-263. https://doi.org/10.1016/j.ymgme.2004.08.008
  31. Stowe RC, Agarwal S. Novel PEX26 Mutation Causing Zellweger Syndrome Presenting as Feeding Intolerance and Hypotonia. Pediatric Neurology. 2017;75:96-97. https://doi.org/10.1016/j.pediatrneurol.2017.06.012
  32. Tanaka AJ, Okumoto K, Tamura S, Abe Y, Hirsch Y, Deng L, Ekstein J, Chung WK, Fujiki Y. A newly identified mutation in the PEX26 gene is associated with a milder form of Zellweger spectrum disorder. Cold Spring Harbor Molecular Case Studies. 2019;5(1):a003483. https://doi.org/10.1101/mcs.a003483
  33. Weller S, Cajigas I, Morrell J, Obie C, Steel G, Gould SJ, Valle D. Alternative Splicing Suggests Extended Function of PEX26 in Peroxisome Biogenesis. American Journal of Human Genetics. 2005;76(6):987-1007. https://doi.org/10.1086/430637
  34. Waterham HR, Ebberink MS. Genetics and molecular basis of human peroxisome biogenesis disorders. Biochimica et Biophysica Acta. 2012;1822(9):1430-1441. https://doi.org/10.1016/j.bbadis.2012.04.006
  35. Girzalsky W, Saffian D, Erdmann R. Peroxisomal protein translocation. Biochimica et Biophysica Acta. 2010;1803(6):724-731. https://doi.org/10.1016/j.bbamcr.2010.01.002
  36. Nazarko TY. Pexophagy is responsible for 65% of cases of peroxisome biogenesis disorders. Autophagy. 2017;13(5):991-994. https://doi.org/10.1080/15548627.2017.1291480
  37. Guder P, Lotz-Havla AS, Woidy M, Reiß DD, Danecka MK, Schatz UA, Becker M, Ensenauer R, Pagel P, Büttner L, Muntau AC, Gersting SW. Isoform-specific domain organization determines conformation and function of the peroxisomal biogenesis factor PEX26. Biochimica et Biophysica Acta. Molecular Cell Research. 2019;1866(3):518-531. https://doi.org/10.1016/j.bbamcr.2018.10.013
  38. Matsumoto N, Tamura S, Fujiki Y. The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes. Nature Cell Biology. 2003;5(5):454-460. https://doi.org/10.1038/ncb982
  39. Tamura S, Matsumoto N, Takeba R, Fujiki Y. AAA peroxins and their recruiter Pex26p modulate the interactions of peroxins involved in peroxisomal protein import. Journal of Biological Chemistry. 2014;289(35):24336-24346. https://doi.org/10.1074/jbc.M114.588038
  40. Klouwer FC, Berendse K, Ferdinandusse S, Wanders RJ, Engelen M, Poll-The BT. Zellweger spectrum disorders: clinical overview and management approach. Orphanet Journal of Rare Diseases. 2015;10:151. https://doi.org/10.1186/s13023-015-0368-9
  41. Enns GM, Ammous Z, Himes RW, Nogueira J, Palle S, Sullivan M, Ramirez C. Diagnostic challenges and disease management in patients with a mild Zellweger spectrum disorder phenotype. Molecular Genetics and Metabolism. 2021;134(3):217-222. https://doi.org/10.1016/j.ymgme.2021.09.007
  42. Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews®. Seattle (WA): University of Washington; 1993-2024.
  43. Fujiki Y, Abe Y, Imoto Y, Tanaka AJ, Okumoto K, Honsho M, Tamura S, Miyata N, Yamashita T, Chung WK, Kuroiwa T. Recent insights into peroxisome biogenesis and associated diseases. Journal of Cell Science. 2020;133(9):jcs236943. https://doi.org/10.1242/jcs.236943
  44. Weller S, Gould SJ, Valle D. Peroxisome biogenesis disorders. Annual Review of Genomics and Human Genetics. 2003;4:165-211. https://doi.org/10.1146/annurev.genom.4.070802.110424
  45. Bousfiha A, Bakhchane A, Charoute H, Riahi Z, Snoussi K, Rouba H, Bonnet C, Petit C, Barakat A. A novel PEX1 mutation in a Moroccan family with Zellweger spectrum disorders. Human Genome Variation. 2017;4:17009. https://doi.org/10.1038/hgv.2017.9
  46. Cheillan D. Zellweger Syndrome Disorders: From Severe Neonatal Disease to Atypical Adult Presentation. Advances in Experimental Medicine and Biology. 2020;1299:71-80. https://doi.org/10.1007/978-3-030-60204-8_6
  47. Percy AK, Rutledge SL. Adrenoleukodystrophy and related disorders. Mental Retardation and Developmental Disabilities Research Reviews. 2001;7(3):179-189. https://doi.org/10.1002/mrdd.1026
  48. Ratbi I, Falkenberg KD, Sommen M, Al-Sheqaih N, Guaoua S, Vandeweyer G, Urquhart JE, Chandler KE, Williams SG, Roberts NA, El Alloussi M, Black GC, Ferdinandusse S, Ramdi H, Heimler A, Fryer A, Lynch SA, Cooper N, Ong KR, Smith CE, Inglehearn CF, Mighell AJ, Elcock C, Poulter JA, Tischkowitz M, Davies SJ, Sefiani A, Mironov AA, Newman WG, Waterham HR, Van Camp G. Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6. American Journal of Human Genetics. 2015;97(4):535-545. https://doi.org/10.1016/j.ajhg.2015.08.011
  49. Yik WY, Steinberg SJ, Moser AB, Moser HW, Hacia JG. Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. Human Mutation. 2009;30(3):E467-480. https://doi.org/10.1002/humu.20932
  50. Preuss N, Brosius U, Biermanns M, Muntau AC, Conzelmann E, Gartner J. PEX1 mutations in complementation group 1 of Zellweger spectrum patients correlate with severity of disease. Pediatric Research. 2002;51(6):706-714. https://doi.org/10.1203/00006450-200206000-00008
  51. Kurokawa Y, Honma Y, Sawaki A, Naito Y, Iwagami S, Komatsu Y, Takahashi T, Nishida T, Doi T. Pimitespib in patients with advanced gastrointestinal stromal tumor (CHAPTER-GIST-301): a randomized, double-blind, placebo-controlled phase III trial. Annals of Oncology. 2022;33(9):959-967. https://doi.org/10.1016/j.annonc.2022.05.518
  52. Du CY, Zhou Y, Song C, Wang YP, Jie ZG, He YL, Liang XB, Cao H, Yan ZS, Shi YQ. Is there a role of surgery in patients with recurrent or metastatic gastrointestinal stromal tumours responding to imatinib: A prospective randomised trial in China. European Journal of Cancer. 2014;50(10):1772-1778. https://doi.org/10.1016/j.ejca.2014.03.280
  53. McAuliffe JC, Hunt KK, Lazar AJ, Choi H, Qiao W, Thall P, Pollock RE, Benjamin RS, Trent JC. A Randomized, Phase II Study of Preoperative plus Postoperative Imatinib in GIST: Evidence of Rapid Radiographic Response and Temporal Induction of Tumor Cell Apoptosis. Annals of Surgical Oncology. 2009;16(4):910-919. https://doi.org/10.1245/s10434-008-0177-7
  54. Corless CL, Ballman KV, Antonescu C, Blanke CD, Blackstein ME, Demetri GD, von Mehren M, Maki RG, Pisters PW, DeMatteo RP. Relation of tumor pathologic and molecular features to outcome after surgical resection of localized primary gastrointestinal stromal tumor (GIST): Results of the intergroup phase III trial ACOSOG Z9001. Journal of Clinical Oncology. 2010;28(15 Suppl):10006-10006. https://doi.org/10.1200/jco.2010.28.15_suppl.10006
  55. Cousin S. A Phase I/II Study of Regorafenib Plus Avelumab in Solid Tumors (REGOMUNE). Accessed August 20, 2024. https://clinicaltrials.gov/study/NCT03475953#more-information
  56. Efficacy and Safety of Famitinib Versus Sunitinib in the Treatment of Advanced Gastrointestinal Stromal Tumour Patients After Failure of Imatinib. Accessed August 20, 2024. https://clinicaltrials.gov/study/NCT0440922
  57. Cogent Biosciences. (Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors. Accessed August 20, 2024. https://clinicaltrials.gov/ct2/show/NCT05208047
  58. Matsumoto S, Takayama T, Wakatsuki K, Enomoto K, Tanaka T, Migita K, Takano M, Nakajima Y. An esophageal gastrointestinal stromal tumor with regional lymph node metastasis. Esophagus. 2010;7(2):115-118. https://doi.org/10.1007/s10388-010-0231-y
  59. Koyanagi K, Nakagawa M, Ozawa S, Nagase T, Seishima R, Kanai T. Thoracoscopic enucleation for small-sized gastrointestinal stromal tumor of the esophagus: report of two cases. Esophagus. 2010;7(4):219-224. https://doi.org/10.1007/s10388-010-0243-7
  60. Masuda T, Toh Y, Kabashima A, Aoki Y, Harimoto N, Ito S, Taomoto J, Ikeda O, Ohga T, Adachi E, Sakaguchi Y, Hirahashi M, Nishiyama K, Okamura T. Overt lymph node metastases from a gastrointestinal stromal tumor of the esophagus. Journal of Thoracic and Cardiovascular Surgery. 2007;134(3):810-811. https://doi.org/10.1016/j.jtcvs.2007.06.002
  61. Kobayashi H, Kiguchi G, Miki A, Uryuhara K, Okada N, Kaihara S, Imai Y, Hosotani R. A case report of giant esophageal gastrointestinal stromal tumor surgically resected after preoperative imatinib treatment. Esophagus. 2011;8(2):119-124. https://doi.org/10.1007/s10388-011-0264-x
  62. Sato H, Kanda T, Hirota S, Bamba T, Sakamoto K, Kosugi SI, Matsuki A, Mashima Y, Watanabe G, Hatakeyama K. Surgical resection of gastrointestinal stromal tumor of esophagus following preoperative imatinib treatment: a case report. Esophagus. 2010;7(1):65-69. https://doi.org/10.1007/s10388-009-0217-9
  63. Miettinen M, Sobin LH, Lasota J. Gastrointestinal Stromal Tumors of the Stomach. American Journal of Surgical Pathology. 2005;29(1):52-68. https://doi.org/10.1097/01.pas.0000146010.92933
  64. Luo Y, Wu Y, Chang X, Huang B, Luo D, Zhang J, Zhang P, Shi H, Fan J, Nie X. Identification of a novel FGFR2-KIAA1217 fusion in esophageal gastrointestinal stromal tumours: A case report. Frontiers in Oncology. 2022;12. https://doi.org/10.3389/fonc.2022.884814
  65. Haller F, Moskalev EA, Faucz FR, Barthelmeß S, Wiemann S, Bieg M, Assie G, Bertherat J, Schaefer IM, Otto C, Rattenberry E, Maher ER, Ströbel P, Werner M, Carney JA, Hartmann A, Stratakis CA, Agaimy A. Aberrant DNA hypermethylation of SDHC: a novel mechanism of tumor development in Carney triad. Endocrine-Related Cancer. 2014;21(4):567-577. https://doi.org/10.1530/ERC-14-0254
  66. Zhang L, Smyrk TC, Young WF, Stratakis CA, Carney JA. Gastric Stromal Tumors in Carney Triad Are Different Clinically, Pathologically, and Behaviorally From Sporadic Gastric Gastrointestinal Stromal Tumors: Findings in 104 Cases. American Journal of Surgical Pathology. 2010;34(1):53-64. https://doi.org/10.1097/PAS.0b013e3181c20f4f
  67. Ricci R, Martini M, Cenci T, Carbone A, Lanza P, Biondi A, Rindi G, Cassano A, Larghi A, Persiani R, Larocca LM. PDGFRA-mutant syndrome. Modern Pathology. 2015;28(7):954-964. https://doi.org/10.1038/modpathol.2015.56
  68. Arita A, Takahashi T, Nakajima K, Kurokawa Y, Hirota S, Nishida T, Yamashita K, Saito T, Tanaka K, Makino T, Yamasaki M, Kawai K, Motoyama Y, Morii E, Eguchi H, Doki Y. Surgery for multiple gastric gastrointestinal stromal tumors and large esophageal diverticulum related to germline mutation of the KIT gene: a case report. Surgical Case Reports. 2023;9(1):183. https://doi.org/10.1186/s40792-023-01766-w
  69. Bachet JB, Landi B, Laurent-Puig P, Italiano A, Le Cesne A, Lévy P, Safar V, Duffaud F, Blay JY, Emile JF. Diagnosis, prognosis and treatment of patients with gastrointestinal stromal tumour (GIST) and germline mutation of KIT exon 13. European Journal of Cancer. 2013;49(11):2531-2541. https://doi.org/10.1016/j.ejca.2013.04.005
  70. Ohshima K, Fujiya K, Nagashima T, Ohnami S, Hatakeyama K, Urakami K, Naruoka A, Watanabe Y, Moromizato S, Shimoda Y, Ohnami S, Serizawa M, Akiyama Y, Kusuhara M, Mochizuki T, Sugino T, Shiomi A, Tsubosa Y, Uesaka K, Terashima M, Yamaguchi K. Driver gene alterations and activated signaling pathways toward malignant progression of gastrointestinal stromal tumors. Cancer Science. 2019;110(12):3821-3833. https://doi.org/10.1111/cas.14202
  71. Joensuu H, Eriksson M, Hall KS, Hartmann JT, Pink D, Schütte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Ballman KV, Leinonen M, DeMatteo RP, Reichardt P. Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. Cancer. 2014;120(15):2325-2333. https://doi.org/10.1002/cncr.28669
  72. Rubió-Casadevall J, Borràs JL, Carmona-García MC, Ameijide A, Gonzalez-Vidal A, Ortiz MR, Bosch R, Riu F, Parada D, Martí E, Miró J, Sirvent JJ, Galceran J, Marcos-Gragera R. Correlation between mutational status and survival and second cancer risk assessment in patients with gastrointestinal stromal tumors: a population-based study. World Journal of Surgical Oncology. 2015;13(1):47. https://doi.org/10.1186/s12957-015-0474-0
  73. Joensuu H, Rutkowski P, Nishida T, Steigen SE, Brabec P, Plank L, Nilsson B, Braconi C, Bordoni A, Magnusson MK, Sufliarsky J, Federico M, Jonasson JG, Hostein I, Bringuier PP, Emile JF. KIT and PDGFRA Mutations and the Risk of GI Stromal Tumor Recurrence. Journal of Clinical Oncology. 2015;33(6):634-642. https://doi.org/10.1200/JCO.2014.57.4970
  74. Park JW, Cho CH, Jeong DS, Chae HD. Role of 18F-fluoro-2-deoxyglucose Positron Emission Tomography in Gastric GIST: Predicting Malignant Potential Pre-operatively. Journal of Gastric Cancer. 2011;11(3):173-179. https://doi.org/10.5230/jgc.2011.11.3.173
  75. Dendy M, Johnson K, Boffa DJ. Spectrum of FDG uptake in large (>10 cm) esophageal leiomyomas. Journal of Thoracic Disease. 2015;7(12):E648-E651. https://doi.org/10.3978/j.issn.2072-1439.2015.11.64
  76. Săftoiu A. Endoscopic ultrasound-guided fine needle aspiration biopsy for the molecular diagnosis of gastrointestinal stromal tumors: shifting treatment options. Journal of Gastrointestinal and Liver Diseases. 2008;17(2):131-133.
  77. Lott S, Schmieder M, Mayer B, Henne-Bruns D, Knippschild U, Agaimy A, Schwab M, Kramer K. Gastrointestinal stromal tumors of the esophagus: evaluation of a pooled case series regarding clinicopathological features and clinical outcome. American Journal of Cancer Research. 2015;5(1):333-343.
  78. Stelow EB, Stanley MW, Lai R, Mallery S. Endoscopic Ultrasound-Guided Fine-Needle Aspiration Findings of Gastrointestinal Leiomyomas and Gastrointestinal Stromal Tumors. American Journal of Clinical Pathology. 2003;119(5):703-708. https://doi.org/10.1309/UWUV-Q001-0D9W-0HPN
  79. Nemeth K, Williams C, Rashid M, Robinson M, Rasheed A. Oesophageal GIST—A rare breed case report and review of the literature. International Journal of Surgery Case Reports. 2015;10: 256-259. https://doi.org/10.1016/j.ijscr.2015.02.023
  80. Lasota J, Miettinen M. Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology. 2008;53(3):245-266. https://doi.org/10.1111/j.1365-2559.2008.02977.x
  81. Gold JS, Gönen M, Gutiérrez A, Broto JM, García-del-Muro X, Smyrk TC, Maki RG, Singer S, Brennan MF, Antonescu CR, Donohue JH, DeMatteo RP. Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis. The Lancet Oncology. 2009;10(11):1045-1052. https://doi.org/10.1016/S1470-2045(09)70242-6
  82. Wozniak A, Rutkowski P, Piskorz A, Ciwoniuk M, Osuch C, Bylina E, Sygut J, Chosia M, Rys J, Urbanczyk K, Kruszewski W, Sowa P, Siedlecki J, Debiec-Rychter M, Limon J; Polish Clinical GIST Registry. Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience. Annals of Oncology. 2012;23(2):353-360. https://doi.org/10.1093/annonc/mdr127
  83. Yamamoto H, Ebihara Y, Tanaka K, Matsui A, Nakanishi Y, Asano T, Noji T, Kurashima Y, Murakami S, Nakamura T, Tsuchikawa T, Okamura K, Shichinohe T, Hirano S. Robot-assisted thoracoscopic esophagectomy for gastrointestinal stromal tumor of the esophagus: A case report. International Journal of Surgery Case Reports. 2021;86:106335. https://doi.org/10.1016/j.ijscr.2021.106335
  84. Marqueen KE, Moshier E, Buckstein M, Ang C. Neoadjuvant therapy for gastrointestinal stromal tumors: A propensity score‐weighted analysis. International Journal of Cancer. 2021;149(1):177-185. https://doi.org/10.1002/ijc.33536
  85. Wang D, Zhang Q, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M, Eisenberg BL. Phase II Trial of Neoadjuvant/adjuvant Imatinib Mesylate for Advanced Primary and Metastatic/recurrent Operable Gastrointestinal Stromal Tumors: Long-term Follow-up Results of Radiation Therapy Oncology Group 0132. Annals of Surgical Oncology. 2012;19(4):1074-1080. https://doi.org/10.1245/s10434-011-2190-5
  86. Nishida T, Kanda T, Nishitani A, Takahashi T, Nakajima K, Ishikawa T, Hirota S. Secondary mutations in the kinase domain of the KIT gene are predominant in imatinib‐resistant gastrointestinal stromal tumor. Cancer Science. 2008;99(4):799-804. https://doi.org/10.1111/j.1349-7006.2008.00727.x
  87. Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D, Singer S, Brennan MF, Maki RG, DeMatteo RP. Acquired Resistance to Imatinib in Gastrointestinal Stromal Tumor Occurs Through Secondary Gene Mutation. Clinical Cancer Research. 2005;11(11):4182-4190. https://doi.org/10.1158/1078-0432.CCR-04-2245
  88. See full prescribing information for VITRAKVI. Accessed September 10, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211710s000lbl.pdf
  89. US Food and Drug Administration. Prescribing information — Rozlytrek. Accessed September 10, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212725s000lbl.pdf
  90. Yebra M, Bhargava S, Kumar A, Burgoyne AM, Tang CM, Yoon H, Banerjee S, Aguilera J, Cordes T, Sheth V, Noh S, Ustoy R, Li S, Advani SJ, Corless CL, Heinrich MC, Kurzrock R, Lippman SM, Fanta PT, Harismendy O, Metallo C, Sicklick JK. Establishment of Patient-Derived Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumor Models for Predicting Therapeutic Response. Clinical Cancer Research. 2022;28(1):187-200. https://doi.org/10.1158/1078-0432.CCR-21-2092
  91. Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST). Accessed September 10, 2024. https://clinicaltrials.gov/study/NCT03556384
  92. Dhillon S. Ripretinib: First Approval. Drugs. 2020;80(11):1133-1138. https://doi.org/10.1007/s40265-020-01348-2
  93. See full prescribing information for QINLOCK. Accessed September 10, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213973s000lbl.pdf
  94. US Food and Drug Administration. FDA approves avapritinib for gastrointestinal stromal tumor with a rare mutation. Accessed September 10, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-avapritinib-gastrointestinal-stromal-tumor-rare-mutation
  95. Chi P, Qin LX, Nguyen B, Kelly CM, D’Angelo SP, Dickson MA, Gounder MM, Keohan ML, Movva S, Nacev BA, Rosenbaum E, Thornton KA, Crago AM, Yoon S, Ulaner G, Yeh R, Martindale M, Phelan HT, Biniakewitz MD, Warda S, Lee CJ, Berger MF, Schultz ND, Singer S, Hwang S, Chen Y, Antonescu CR, Tap WD. Phase II Trial of Imatinib Plus Binimetinib in Patients With Treatment-Naive Advanced Gastrointestinal Stromal Tumor. Journal of Clinical Oncology. 2022;40(9):997-1008. https://doi.org/10.1200/JCO.21.02029
  96. US National Library of Medicine. A study of pimitespib in combination with imatinib in patients with GIST (CHAPTER-GIST-101). Accessed September 10, 2024. https://www.clinicaltrials.gov/ct2/show/NCT05245968
  97. Joensuu H, Blay JY, Comandone A, Martin-Broto J, Fumagalli E, Grignani G, Del Muro XG, Adenis A, Valverde C, Pousa AL, Bouché O, Italiano A, Bauer S, Barone C, Weiss C, Crippa S, Camozzi M, Castellana R, Le Cesne A. Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib. British Journal of Cancer. 2017;117(9):1278-1285. https://doi.org/10.1038/bjc.2017.290
  98. Adis insight. Gastrointestinal stromal tumours. Accessed September 10, 2024. https://adisinsight.springer.com/drugs/800063657
  99. US National Library of Medicine. A phase I/II study of regorafenib plus avelumab in solid tumors (REGOMUNE). Accessed September 10, 2024. https://clinicaltrials.gov/ct2/show/NCT03475953
  100. US National Library of Medicine. PDR001 plus imatinib for metastatic or unresectable GIST. Accessed September 10, 2024. https://clinicaltrials.gov/ct2/show/NCT03609424
  101. Call J, Walentas C, Eickhoff JC, Scherzer N. Survival of gastrointestinal stromal tumor patients in the imatinib era: life raft group observational registry. BMC Cancer. 2012;12(1):90. https://doi.org/10.1186/1471-2407-12-90
  102. Miettinen M, Lasota J. Gastrointestinal stromal tumors: Pathology and prognosis at different sites. Seminars in Diagnostic Pathology. 2006;23(2):70-83. https://doi.org/10.1053/j.semdp.2006.09.001
  103. IJzerman NS, van Werkhoven E, Mohammadi M, Hollander DD, Bleckman RF, Reyners AKL, Desar IME, Gelderblom H, Grünhagen DJ, Mathijssen RHJ, Steeghs N, van der Graaf WTA. Sex differences in patients with gastrointestinal stromal tumours: do they exist and does it affect survival? ESMO Open. 2022;7(6):100649. https://doi.org/10.1016/j.esmoop.2022.100649
  104. Volchenko NS, Mamontov AS, Goeva NS. Rare esophageal tumors. Onkologiya. P.A. Herzen Journal of Oncology. 2019;8(6):453. https://doi.org/10.17116/onkolog20198061453
  105. Cohen C, Pop D, Icard P, Berthet JP, Venissac N, Mouroux J. Is There a Place for Thoracoscopic Enucleation of Esophageal Gastrointestinal Stromal Tumors? The Thoracic and Cardiovascular Surgeon. 2019;67(07):585-588. https://doi.org/10.1055/s-0038-1670662
  106. Keung EZ, Raut CP. Management of Gastrointestinal Stromal Tumors. Surgical Clinics of North America. 2017;97(2):437-452. https://doi.org/10.1016/j.suc.2016.12.001
  107. Gronchi A, Raut CP. The Combination of Surgery and Imatinib in GIST: A Reality for Localized Tumors at High Risk, an Open Issue for Metastatic Ones. Annals of Surgical Oncology. 2012;19(4): 1051-1055. https://doi.org/10.1245/s10434-011-2191-4
  108. Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D, Fletcher CD, Demetri GD, Bertagnolli MM. Surgical Management of Advanced Gastrointestinal Stromal Tumors After Treatment With Targeted Systemic Therapy Using Kinase Inhibitors. Journal of Clinical Oncology. 2006;24(15):2325-2331. https://doi.org/10.1200/JCO.2005.05.3439
  109. Blackstein ME, Blay JY, Corless C, Driman DK, Riddell R, Soulières D, Swallow CJ, Verma S; Canadian Advisory Committee on GIST. Gastrointestinal Stromal Tumours: Consensus Statement on Diagnosis and Treatment. Canadian Journal of Gastroenterology. 2006;20(3):157-163. https://doi.org/10.1155/2006/434761
  110. DeMatteo RP, Maki RG, Singer S, Gonen M, Brennan MF, Antonescu CR. Results of Tyrosine Kinase Inhibitor Therapy Followed by Surgical Resection for Metastatic Gastrointestinal Stromal Tumor. Annals of Surgery. 2007;245(3):347-352. https://doi.org/10.1097/01.sla.0000236630.93587.59
  111. Klug LR, Khosroyani HM, Kent JD, Heinrich MC. New treatment strategies for advanced-stage gastrointestinal stromal tumours. Nature Reviews Clinical Oncology. 2022;19(5):328-341. https://doi.org/10.1038/s41571-022-00606-4
  112. A phase 1, multicenter, open-label, first-in-human study of DS-6157a in patients (pts) with advanced gastrointestinal stromal tumor (GIST). Accessed September 10, 2024. https://meetings.asco.org/abstracts-presentations/208008
  113. DS-6157a in Participants with Advanced Gastrointestinal Stromal Tumor (GIST). Accessed September 10, 2024. https://clinicaltrials.gov/ct2/show/NCT04276415
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