دورية أكاديمية
Alternative lengthening of telomeres (ALT) in pediatric high-grade gliomas can occur without ATRX mutation and is enriched in patients with pathogenic germline mismatch repair (MMR) variants.
العنوان: | Alternative lengthening of telomeres (ALT) in pediatric high-grade gliomas can occur without ATRX mutation and is enriched in patients with pathogenic germline mismatch repair (MMR) variants. |
---|---|
المؤلفون: | Stundon JL; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania,USA., Ijaz H; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania,USA., Gaonkar KS; Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Department of Bioinformatics and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Kaufman RS; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Department of Bioinformatics and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Jin R; Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Karras A; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Vaksman Z; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Department of Bioinformatics and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Kim J; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland,USA., Corbett RJ; Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Lueder MR; Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Miller DP; Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Guo Y; Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Santi M; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Li M; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Lopez G; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Storm PB; Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Resnick AC; Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Waanders AJ; Division of Hematology, Oncology, NeuroOncology, and Stem Cell Transplant, Ann & Robert H Lurie Children's Hospital of Chicago, Illinois,USA.; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois,USA., MacFarland SP; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania,USA., Stewart DR; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland,USA., Diskin SJ; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania,USA.; Department of Bioinformatics and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania,USA., Rokita JL; Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Department of Bioinformatics and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA., Cole KA; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,USA.; Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania,USA.; Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania,USA. |
المصدر: | Neuro-oncology [Neuro Oncol] 2023 Jul 06; Vol. 25 (7), pp. 1331-1342. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 100887420 Publication Model: Print Cited Medium: Internet ISSN: 1523-5866 (Electronic) Linking ISSN: 15228517 NLM ISO Abbreviation: Neuro Oncol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2010- : Oxford : Oxford University Press Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub., |
مواضيع طبية MeSH: | Glioma*/genetics , Brain Neoplasms*/genetics , Brain Neoplasms*/pathology, Humans ; Child ; DNA Mismatch Repair ; Telomere Homeostasis/genetics ; X-linked Nuclear Protein/genetics ; Mutation ; Telomere/genetics ; Telomere/pathology |
مستخلص: | Background: To achieve replicative immortality, most cancers develop a telomere maintenance mechanism, such as reactivation of telomerase or alternative lengthening of telomeres (ALT). There are limited data on the prevalence and clinical significance of ALT in pediatric brain tumors, and ALT-directed therapy is not available. Methods: We performed C-circle analysis (CCA) on 579 pediatric brain tumors that had corresponding tumor/normal whole genome sequencing through the Open Pediatric Brain Tumor Atlas (OpenPBTA). We detected ALT in 6.9% (n = 40/579) of these tumors and completed additional validation by ultrabright telomeric foci in situ on a subset of these tumors. We used CCA to validate TelomereHunter for computational prediction of ALT status and focus subsequent analyses on pediatric high-grade gliomas (pHGGs) Finally, we examined whether ALT is associated with recurrent somatic or germline alterations. Results: ALT is common in pHGGs (n = 24/63, 38.1%), but occurs infrequently in other pediatric brain tumors (<3%). Somatic ATRX mutations occur in 50% of ALT+ pHGGs and in 30% of ALT- pHGGs. Rare pathogenic germline variants in mismatch repair (MMR) genes are significantly associated with an increased occurrence of ALT. Conclusions: We demonstrate that ATRX is mutated in only a subset of ALT+ pHGGs, suggesting other mechanisms of ATRX loss of function or alterations in other genes may be associated with the development of ALT in these patients. We show that germline variants in MMR are associated with the development of ALT in patients with pHGG. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.) |
التعليقات: | Comment in: Neuro Oncol. 2023 Jul 6;25(7):1343-1344. doi: 10.1093/neuonc/noad054. (PMID: 36883676) |
References: | Cell Rep. 2021 Dec 7;37(10):110088. (PMID: 34879271) PLoS One. 2018 Sep 18;13(9):e0204159. (PMID: 30226859) Nat Rev Cancer. 2022 Sep;22(9):515-532. (PMID: 35790854) Cell Rep. 2022 Apr 5;39(1):110602. (PMID: 35385755) J Med Genet. 2022 Apr;59(4):318-327. (PMID: 33622763) Neuro Oncol. 2020 Jan 11;22(1):163-165. (PMID: 31613963) Nat Commun. 2021 Mar 10;12(1):1552. (PMID: 33692341) Neurooncol Adv. 2021 Apr 19;3(1):vdab061. (PMID: 34056608) Nat Genet. 2017 Mar;49(3):349-357. (PMID: 28135248) Neoplasia. 2023 Jan;35:100846. (PMID: 36335802) Mol Cell. 2021 Mar 4;81(5):1027-1042.e4. (PMID: 33453166) FEBS Lett. 2010 Sep 10;584(17):3800-11. (PMID: 20542034) Acta Neuropathol. 2014 Dec;128(6):853-62. (PMID: 25315281) Sci Transl Med. 2016 Mar 2;8(328):328ra28. (PMID: 26936505) J Med Genet. 2014 Jun;51(6):355-65. (PMID: 24737826) Sci Rep. 2018 Jan 22;8(1):1300. (PMID: 29358629) Childs Nerv Syst. 2021 Mar;37(3):809-818. (PMID: 33128602) J Neurooncol. 2017 Nov;135(2):381-390. (PMID: 28755323) Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230) Cell. 2020 Dec 23;183(7):1962-1985.e31. (PMID: 33242424) Mod Pathol. 2013 Nov;26(11):1425-32. (PMID: 23765250) J Neuropathol Exp Neurol. 2010 Jul;69(7):729-36. (PMID: 20535033) Nat Commun. 2020 Feb 5;11(1):733. (PMID: 32024817) PLoS One. 2015 Apr 29;10(4):e0125201. (PMID: 25923330) Methods. 2017 Feb 1;114:74-84. (PMID: 27595911) Cancer Res. 2022 Sep 16;82(18):3345-3358. (PMID: 35947641) Trends Cancer. 2015 Oct 1;1(2):145-156. (PMID: 26645051) Nucleic Acids Res. 2018 Jun 1;46(10):4903-4918. (PMID: 29718321) STAR Protoc. 2021 May 31;2(2):100569. (PMID: 34136834) Nat Commun. 2021 Feb 24;12(1):1269. (PMID: 33627664) Oncogene. 2002 Jan 21;21(4):598-610. (PMID: 11850785) Sci Transl Med. 2021 Aug 18;13(607):. (PMID: 34408079) Nucleic Acids Res. 2014 May;42(9):e75. (PMID: 24609383) Oncologist. 2017 Dec;22(12):1478-1490. (PMID: 28912153) Am J Pathol. 2011 Oct;179(4):1608-15. (PMID: 21888887) Nat Med. 1997 Nov;3(11):1198-9. (PMID: 9359690) Nature. 2001 Jun 7;411(6838):713-6. (PMID: 11395777) BMC Bioinformatics. 2019 May 28;20(1):272. (PMID: 31138115) Cell. 2012 Feb 17;148(4):651-63. (PMID: 22341440) Trends Genet. 2017 Dec;33(12):921-932. (PMID: 28969871) Cell. 2017 Nov 16;171(5):1042-1056.e10. (PMID: 29056344) Neuro Oncol. 2019 Aug 5;21(8):968-980. (PMID: 30805642) Expert Opin Ther Targets. 2018 Jul;22(7):599-613. (PMID: 29889582) Nature. 2012 Jan 29;482(7384):226-31. (PMID: 22286061) Aging Cell. 2009 Feb;8(1):2-17. (PMID: 18986375) Mol Cancer Res. 2019 Dec;17(12):2480-2491. (PMID: 31611308) |
معلومات مُعتمدة: | U2C-CA233285 United States NH NIH HHS; HHSN261200800001C United States CA NCI NIH HHS; K12 HD043245 United States HD NICHD NIH HHS; T32 CA009615 United States CA NCI NIH HHS; HHSN261200800001E United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: ATRX; Telomere; alternative lengthening of telomeres; mismatch repair; pHGG; pediatric brain tumors |
المشرفين على المادة: | EC 3.6.4.12 (X-linked Nuclear Protein) EC 3.6.4.12 (ATRX protein, human) |
تواريخ الأحداث: | Date Created: 20221221 Date Completed: 20230710 Latest Revision: 20240615 |
رمز التحديث: | 20240615 |
مُعرف محوري في PubMed: | PMC10326481 |
DOI: | 10.1093/neuonc/noac278 |
PMID: | 36541551 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1523-5866 |
---|---|
DOI: | 10.1093/neuonc/noac278 |