دورية أكاديمية

Development and evaluation of INT 2 GRATE: a platform for comprehensive assessment of the role of germline variants informed by tumor signature profile in Lynch syndrome.

التفاصيل البيبلوغرافية
العنوان: Development and evaluation of INT 2 GRATE: a platform for comprehensive assessment of the role of germline variants informed by tumor signature profile in Lynch syndrome.
المؤلفون: Isidro RA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States.; Harvard Medical School, Boston, MA, United States., Chittenden A; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, United States., Walker M; Division of Genetics, Brigham and Women's Hospital, Boston, MA, United States., Schwartz A; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, United States., Koeller DR; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, United States., Hayes CP; Division of Genetics, Brigham and Women's Hospital, Boston, MA, United States., Unal B; Division of Genetics, Brigham and Women's Hospital, Boston, MA, United States., Manam MD; Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States., Buehler RM; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, United States., Manning DK; Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States., Sholl LM; Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States.; Harvard Medical School, Boston, MA, United States., Redston MS; Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States.; Harvard Medical School, Boston, MA, United States., Yurgelun MB; Harvard Medical School, Boston, MA, United States.; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, United States.; Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, United States., Rana HQ; Harvard Medical School, Boston, MA, United States.; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, United States.; Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, United States., Garber JE; Harvard Medical School, Boston, MA, United States.; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, United States.; Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, United States., Ghazani AA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States.; Harvard Medical School, Boston, MA, United States.; Division of Genetics, Brigham and Women's Hospital, Boston, MA, United States.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States.
المصدر: Frontiers in oncology [Front Oncol] 2024 Jan 24; Vol. 13, pp. 1284690. Date of Electronic Publication: 2024 Jan 24 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مستخلص: The presence of variants of uncertain significance (VUS) in DNA mismatch repair (MMR) genes leads to uncertainty in the clinical management of patients being evaluated for Lynch syndrome (LS). Currently, there is no platform to systematically use tumor-derived evidence alongside germline data for the assessment of VUS in relation to LS. We developed INT 2 GRATE (INTegrated INTerpretation of GeRmline And Tumor gEnomes) to leverage information from the tumor genome to inform the potential role of constitutional VUS in MMR genes. INT 2 GRATE platform has two components: a comprehensive evidence-based decision tree that integrates well-established clinico-genomic data from both the tumor and constitutional genomes to help inform the potential relevance of germline VUS in LS; and a web-based user interface (UI). With the INT 2 GRATE decision tree operating in the backend, INT 2 GRATE UI enables the front-end collection of comprehensive clinical genetics and tumor-derived evidence for each VUS to facilitate INT 2 GRATE assessment and data sharing in the publicly accessible ClinVar database. The performance of the INT 2 GRATE decision tree was assessed by qualitative retrospective analysis of genomic data from 5057 cancer patients with MMR alterations which included 52 positive control cases. Of 52 positive control cases with LS and pathogenic MMR alterations, 23 had all the testing parameters for the evaluation by INT 2 GRATE. All these variants were correctly categorized as INT 2 GRATE POSITIVE. The stringent INT 2 GRATE decision tree flagged 29 of positive cases by identifying the absence or unusual presentation of specific evidence, highlighting the conservative INT 2 GRATE logic in favor of a higher degree of confidence in the results. The remaining 99% of cases were correctly categorized as INCONCLUSIVE due to the absence of LS criteria and ≥1 tumor parameters. INT 2 GRATE is an effective platform for clinical and genetics professionals to collect and assess clinical genetics and complimentary tumor-derived information for each germline VUS in suspected LS patients. Furthermore, INT 2 GRATE enables the collation of integrated tumor-derived evidence relevant to germline VUS in LS, and sharing them with a large community, a practice that is needed in precision oncology.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Isidro, Chittenden, Walker, Schwartz, Koeller, Hayes, Unal, Manam, Buehler, Manning, Sholl, Redston, Yurgelun, Rana, Garber and Ghazani.)
References: Cell Rep. 2018 Apr 3;23(1):227-238.e3. (PMID: 29617662)
Nucleic Acids Res. 2003 Jul 1;31(13):3812-4. (PMID: 12824425)
Genet Med. 2020 Jan;22(1):15-25. (PMID: 31337882)
Dis Colon Rectum. 1991 May;34(5):424-5. (PMID: 2022152)
J Genet Couns. 2017 Aug;26(4):866-877. (PMID: 28127677)
Cell. 2018 Apr 5;173(2):291-304.e6. (PMID: 29625048)
Trends Genet. 2019 Jul;35(7):515-526. (PMID: 31128889)
Cancer Prev Res (Phila). 2012 Feb;5(2):320-7. (PMID: 22086678)
N Engl J Med. 1998 Aug 20;339(8):511-8. (PMID: 9709044)
Cell Syst. 2018 Mar 28;6(3):271-281.e7. (PMID: 29596782)
J Natl Compr Canc Netw. 2021 Oct 15;19(10):1122-1132. (PMID: 34666312)
J Clin Oncol. 2008 Dec 10;26(35):5705-12. (PMID: 19001320)
Mod Pathol. 2018 Dec;31(12):1882-1890. (PMID: 29955144)
MethodsX. 2022 Jun 18;9:101761. (PMID: 35774415)
Trans Am Clin Climatol Assoc. 2016;127:81-97. (PMID: 28066040)
Tumori. 2014 May-Jun;100(3):315-20. (PMID: 25076244)
Cancer Cell. 2018 Apr 9;33(4):676-689.e3. (PMID: 29622463)
Ann Oncol. 2013 Nov;24 Suppl 8:viii69-viii74. (PMID: 24131974)
JCO Precis Oncol. 2017;2017:. (PMID: 29850653)
Nucleic Acids Res. 2015 Feb 18;43(3):e19. (PMID: 25428359)
Lancet Oncol. 2011 Jan;12(1):49-55. (PMID: 21145788)
JAMA. 2006 Sep 27;296(12):1469-78. (PMID: 17003395)
Am J Case Rep. 2020 Dec 11;21:e927293. (PMID: 33303731)
J Med Genet. 2019 Jul;56(7):462-470. (PMID: 30877237)
Eur J Cancer. 2015 Mar;51(5):587-94. (PMID: 25673558)
Cell. 2018 Apr 5;173(2):305-320.e10. (PMID: 29625049)
Diagn Pathol. 2017 Mar 04;12(1):24. (PMID: 28259170)
Genet Med. 2018 Feb;20(2):234-239. (PMID: 28749474)
Cancer Cell. 2018 Apr 9;33(4):721-735.e8. (PMID: 29622466)
Psychooncology. 2008 Aug;17(8):822-30. (PMID: 18157792)
Front Genet. 2022 Nov 29;13:1010327. (PMID: 36568376)
Nat Genet. 2021 Nov;53(11):1577-1585. (PMID: 34741162)
J Mol Diagn. 2011 Jan;13(1):93-9. (PMID: 21227399)
PLoS One. 2014 Mar 03;9(3):e90607. (PMID: 24594804)
Genet Med. 2015 May;17(5):405-24. (PMID: 25741868)
Psychooncology. 2009 Oct;18(10):1088-96. (PMID: 19214961)
Gut. 2013 Feb;62(2):272-9. (PMID: 22345660)
Cancer Genet. 2016 Apr;209(4):130-7. (PMID: 26908360)
Hum Mutat. 2017 Mar;38(3):243-251. (PMID: 27995669)
J Clin Oncol. 2011 May 20;29(15):2011-9. (PMID: 21502544)
Genet Med. 2017 Jul;19(7):787-795. (PMID: 28125075)
Gastroenterology. 2010 Jun;138(6):2073-2087.e3. (PMID: 20420947)
Cell. 2018 Apr 5;173(2):400-416.e11. (PMID: 29625055)
Mod Pathol. 2013 Jan;26(1):131-8. (PMID: 22918162)
Nature. 2020 Mar;579(7800):567-574. (PMID: 32214244)
Nat Genet. 2021 Nov;53(11):1523-1525. (PMID: 34741161)
J Clin Oncol. 2017 Jul 1;35(19):2165-2172. (PMID: 28489507)
JAMA. 2006 Sep 27;296(12):1479-87. (PMID: 17003396)
Nucleic Acids Res. 2011 Sep 1;39(17):e118. (PMID: 21727090)
Fam Cancer. 2019 Oct;18(4):465-469. (PMID: 31531760)
Data Brief. 2021 Dec 01;39:107653. (PMID: 34934780)
Bioinformatics. 2009 Nov 1;25(21):2744-50. (PMID: 19734154)
Eur J Med Genet. 2021 Dec;64(12):104359. (PMID: 34628056)
Cancer Epidemiol Biomarkers Prev. 2017 Mar;26(3):404-412. (PMID: 27799157)
Nature. 2012 Jul 18;487(7407):330-7. (PMID: 22810696)
Clin Cancer Res. 2004 Feb 1;10(3):972-80. (PMID: 14871975)
Mod Pathol. 2020 May;33(5):871-879. (PMID: 31857677)
Fam Cancer. 2014 Mar;13(1):1-12. (PMID: 23880961)
J Clin Oncol. 2004 Dec 15;22(24):4934-43. (PMID: 15611508)
Gastroenterology. 1999 Jun;116(6):1453-6. (PMID: 10348829)
Sci Signal. 2013 Apr 02;6(269):pl1. (PMID: 23550210)
N Engl J Med. 2006 Jun 29;354(26):2751-63. (PMID: 16807412)
Front Oncol. 2022 Aug 25;12:942741. (PMID: 36091175)
Nat Commun. 2014;5:3156. (PMID: 24448499)
Cell. 2018 Apr 5;173(2):321-337.e10. (PMID: 29625050)
J Med Genet. 2022 Apr;59(4):328-334. (PMID: 33452216)
Curr Protoc Hum Genet. 2013 Jan;Chapter 7:Unit7.20. (PMID: 23315928)
Ann Surg. 1997 Feb;225(2):202-7. (PMID: 9065297)
J Law Biosci. 2018 Jan 22;4(3):648-657. (PMID: 29868193)
Am J Clin Pathol. 2013 Aug;140(2):177-83. (PMID: 23897252)
Nat Genet. 2019 Feb;51(2):308-318. (PMID: 30643250)
فهرسة مساهمة: Keywords: INT2GRATE; Lynch syndrome; germline VUS; somatic and germline integration; tumor signature profile
تواريخ الأحداث: Date Created: 20240212 Latest Revision: 20240213
رمز التحديث: 20240213
مُعرف محوري في PubMed: PMC10854004
DOI: 10.3389/fonc.2023.1284690
PMID: 38344144
قاعدة البيانات: MEDLINE
الوصف
تدمد:2234-943X
DOI:10.3389/fonc.2023.1284690