Germline SDHB-inactivating mutation in gastric spindle cell sarcoma.
SDH deficiency
gastrointestinal stromal tumor
next-generation sequencing
sarcoma
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
04
04
2020
revised:
12
05
2020
accepted:
30
05
2020
pubmed:
6
6
2020
medline:
19
8
2021
entrez:
6
6
2020
Statut:
ppublish
Résumé
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Inactivating mutations or epigenetic deregulation of succinate dehydrogenase complex (SDH) genes are considered defining features of a subset of GIST occurring in the stomach. Based on comprehensive molecular profiling and biochemical analysis within a precision oncology program, we identified hallmarks of SDH deficiency (germline SDHB-inactivating mutation accompanied by somatic loss of heterozygosity, lack of SDHB expression, global DNA hypermethylation, and elevated succinate/fumarate ratio) in a 40-year-old woman with undifferentiated gastric spindle cell sarcoma that did not meet the diagnostic criteria for other mesenchymal tumors of the stomach, including GIST. These data reveal that the loss of SDH function can be involved in the pathogenesis of non-GIST sarcoma of the gastrointestinal tract.
Substances chimiques
SDHB protein, human
EC 1.3.5.1
Succinate Dehydrogenase
EC 1.3.99.1
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
601-608Informations de copyright
© 2020 Wiley Periodicals, Inc.
Références
von Mehren M, Joensuu H. Gastrointestinal stromal tumors. J Clin Oncol. 2018;36(2):136-143. https://doi.org/10.1200/jco.2017.74.9705.
Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer. 2011;11(12):865-878. https://doi.org/10.1038/nrc3143.
Killian JK, Kim SY, Miettinen M, et al. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor. Cancer Discov. 2013;3(6):648-657. https://doi.org/10.1158/2159-8290.cd-13-0092.
Antonescu CR, Romeo S, Zhang L, et al. Dedifferentiation in gastrointestinal stromal tumor to an anaplastic KIT-negative phenotype. Am J Surg Pathol. 2013;37(3):385-392. https://doi.org/10.1097/pas.0b013e31826c1761.
Li L, Khalili M, Johannes G, et al. Case report of rhabdomyosarcomatous transformation of a primary gastrointestinal stromal tumor (GIST). BMC Cancer. 2019;19(1):1-8. https://doi.org/10.1186/s12885-019-6085-3.
Karakas C, Christensen P, Baek D, Jung M, Ro JY. Dedifferentiated gastrointestinal stromal tumor: recent advances. Ann Diagn Pathol. 2018;39:118-124. https://doi.org/10.1016/j.anndiagpath.2018.12.005.
Malik F, Santiago T, Bahrami A, et al. Dedifferentiation in SDH-deficient gastrointestinal stromal tumor: a report with histologic, immunophenotypic, and molecular characterization. Pediatr Devel Pathol. 2019;22(5):492-498. https://doi.org/10.1177/1093526619846222.
Miettinen M, Lasota J. Succinate dehydrogenase deficient gastrointestinal stromal tumors (GISTs)-a review. Int J Biochem Cell Biol. 2014;53:514-519. https://doi.org/10.1016/j.biocel.2014.05.033.
Pantaleo MA, Lolli C, Nannini M, et al. Good survival outcome of metastatic SDH-deficient gastrointestinal stromal tumors harboring SDHA mutations. Genet Med. 2014;17(5):391-395. https://doi.org/10.1038/gim.2014.115.
Stratakis CA, Carney JA. The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J Intern Med. 2009;266(1):43-52. https://doi.org/10.1111/j.1365-2796.2009.02110.x.
Horak P, Klink B, Heining C, et al. Precision oncology based on omics data: the NCT Heidelberg experience. Int J Cancer. 2017;141(5):877-886. https://doi.org/10.1002/ijc.30828.
Klein RD, Jin L, Rumilla K, Young WF, Lloyd RV. Germline SDHB mutations are common in patients with apparently sporadic sympathetic paragangliomas. Diagno Mol Pathol. 2008;17(2):94-100. https://doi.org/10.1097/pdm.0b013e318150d67c.
Broughton BC, Berneburg M, Fawcett H, et al. Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene. Hum Mol Genet. 2001;10(22):2539-2547. https://doi.org/10.1093/hmg/10.22.2539.
Tokheim C, Karchin R. CHASMplus reveals the scope of somatic missense mutations driving human cancers. Cell Syst. 2019;9(1):9-23. https://doi.org/10.1016/j.cels.2019.05.005.
Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415-421. https://doi.org/10.1038/nature12477.
Davies H, Glodzik D, Morganella S, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med. 2017;23(4):517-525. https://doi.org/10.1038/nm.4292.
Chudasama P, Mughal SS, Sanders MA, et al. Integrative genomic and transcriptomic analysis of leiomyosarcoma. Nat Commun. 2018;9(1):1-5. https://doi.org/10.1038/s41467-017-02602-0.
Wozniak A, Sciot R, Guillou L, et al. Array CGH analysis in primary gastrointestinal stromal tumors: cytogenetic profile correlates with anatomic site and tumor aggressiveness, irrespective of mutational status. Genes Chromosomes Cancer. 2007;46(3):261-276. https://doi.org/10.1002/gcc.20408.
Ässämäki R, Sarlomo-Rikala M, Lopez-Guerrero JA, et al. Array comparative genomic hybridization analysis of chromosomal imbalances and their target genes in gastrointestinal stromal tumors. Genes Chromosomes Cancer. 2007;46(6):564-576. https://doi.org/10.1002/gcc.20439.
Fletcher CDM, Hogendoorn P, Mertens F, Bridge J. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed Lyon, France: IARC Press; 2013.
Italiano A, Mauro ID, Rapp J, et al. Clinical effect of molecular methods in sarcoma diagnosis (GENSARC): a prospective, multicentre, observational study. Lancet Oncol. 2016;17(4):532-538. https://doi.org/10.1016/s1470-2045(15)00583-5.
Ray-Coquard I, Montesco MC, Coindre JM, et al. Sarcoma: concordance between initial diagnosis and centralized expert review in a population-based study within three European regions. Ann Oncol. 2012;23(9):2442-2449. https://doi.org/10.1093/annonc/mdr610.
Dahia PLM, Ross KN, Wright ME, et al. A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet. 2005;1(1):72-80. https://doi.org/10.1371/journal.pgen.0010008.
Xiao M, Yang H, Xu W, et al. Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Gene Dev. 2012;26(12):1326-1338. https://doi.org/10.1101/gad.191056.112.
Niemeijer ND, Papathomas TG, Korpershoek E, et al. Succinate dehydrogenase (SDH)-deficient pancreatic neuroendocrine tumor expands the SDH-related tumor spectrum. J Clin Endocrinol Metab. 2015;100(10):86-93. https://doi.org/10.1210/jc.2015-2689.
Ricketts C, Woodward ER, Killick P, et al. Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst. 2008;100(17):1260-1262. https://doi.org/10.1093/jnci/djn254.
Janeway KA, Kim SY, Lodish M, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci USA. 2011;108(1):314-318. https://doi.org/10.1073/pnas.1009199108.
Flavahan WA, Drier Y, Johnstone SE, et al. Altered chromosomal topology drives oncogenic programs in SDH-deficient GISTs. Nature. 2019;575(7781):229-233. https://doi.org/10.1038/s41586-019-1668-3.
Nolan E, Savas P, Policheni AN, et al. Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer. Sci Transl Med. 2017;9(393):eaal4922. https://doi.org/10.1126/scitranslmed.aal4922.
Assenov Y, Müller F, Lutsik P, Walter J, Lengauer T, Bock C. Comprehensive analysis of DNA methylation data with RnBeads. Nat Methods. 2014;11(11):1138-1140. https://doi.org/10.1038/nmeth.3115.
Kolde R. Pheatmap: pretty heatmaps. R Package. 2015 Jul 2;1(7). https://cran.r-project.org/package=pheatmap.
Richter S, Peitzsch M, Rapizzi E, et al. Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency. J Clin Endocrinol Metabol. 2014;99(10):3903-3911. https://doi.org/10.1210/jc.2014-2151.