Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Open Access

Study Protocol

DNA alterations in ovarian adult granulosa cell tumours: A scoping review protocol

  • Sven Karstensen ,

    Roles Conceptualization, Methodology, Writing – original draft

    sven.hoedt.karstensen@rsyd.dk

    Affiliation Department of Womens’s Health, University of Southern Denmark, Sygehus Sønderjylland, Aabenraa, Denmark

    ⨯
  • Karsten Kaiser,

    Roles Writing – review & editing

    Affiliation Department of Womens’s Health, University of Southern Denmark, Sygehus Sønderjylland, Aabenraa, Denmark

    ⨯
  • Caroline Moos,

    Roles Methodology, Writing – review & editing

    Affiliation Department of Clinical Research, University of Southern Denmark, Sygehus Sønderjylland, Aabenraa, Denmark

    ⨯
  • Tim Svenstrup Poulsen,

    Roles Methodology, Writing – review & editing

    Affiliation Department of Pathology, Molecular Unit, University of Copenhagen, Herlev Hospital, Herlev, Denmark

    ⨯
  • Kirsten Jochumsen,

    Roles Supervision, Writing – review & editing

    Affiliation Department of Gynecology, University of Southern Denmark, Odense University Hospital, Odense, Denmark

    ⨯
  • Claus Høgdall,

    Roles Supervision, Writing – review & editing

    Affiliation Department of Gynecology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark

    ⨯
  • Finn Lauszus,

    Roles Supervision, Writing – review & editing

    Affiliation Department of Womens’s Health, University of Southern Denmark, Sygehus Sønderjylland, Aabenraa, Denmark

    ⨯
  • Estrid Høgdall

    Roles Conceptualization, Methodology, Supervision, Writing – review & editing

    Affiliation Department of Pathology, Molecular Unit, University of Copenhagen, Herlev Hospital, Herlev, Denmark

    ⨯

Abstract

Background

Identifying and describing molecular alterations in tumors has become common with the development of high-throughput sequencing. However, DNA sequencing in rare tumors, such as ovarian adult granulosa cell tumor (aGCT), often lacks statistical power due to the limited number of cases in each study. Questions regarding personalized treatment or prognostic biomarkers for recurrence or other malignancies therefore still need to be elucidated. This scoping review protocol aims to systematically map the current evidence and identify knowledge gaps regarding DNA alterations, actionable variations and prognostic biomarkers in aGCT.

Methods

This scoping review will be conducted based on Arksey and O’Malley’s methodological framework and later modifications by JBI Evidence Synthesis. The protocol complies with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. All original publications describing molecular alterations of aGCT will be included. The search will be performed in May 2024 in the following databases: MEDLINE (Ovid), Embase (Ovid), Web of Science Core Collection and Google Scholar (100-top ranked).

Discussion

This scoping review will identify knowledge and gaps in the current understanding of the molecular landscape of aGCT, clinical trials on actionable variations and priorities for future research. As aGCT are rare, a possible limitation will be the small sample sizes and heterogenic study settings.

Scoping review registration

The review protocol is registered at Open Science Framework under https://doi.org/10.17605/OSF.IO/PX4MF.

Citation: Karstensen S, Kaiser K, Moos C, Poulsen TS, Jochumsen K, Høgdall C, et al. (2024) DNA alterations in ovarian adult granulosa cell tumours: A scoping review protocol. PLoS ONE 19(6): e0303989. https://doi.org/10.1371/journal.pone.0303989

Editor: Gerrit J. Bouma, Western Michigan University School of Medicine: Western Michigan University Homer Stryker MD School of Medicine, UNITED STATES

Received: November 15, 2023; Accepted: May 3, 2024; Published: June 14, 2024

Copyright: © 2024 Karstensen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist

List of abbreviation: aGCT, adult granulosa cell tumor; NGS, next generation sequencing; PeM, Peritoneal Mesothelioma; JBI, Joanna Briggs Insitute; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PCC, Population-Concept-Context

Background

Ovarian adult granulosa cell tumor (aGCT) is a rare tumor arising from the ovarian stroma and accounts for approximately 2–5% of ovarian malignancies [1, 2]. Most aGCTs are diagnosed at an early stage and treated curatively with surgical resection. Unfortunately, approximately 10–20% relapse with advanced tumor spread, sometimes many years after initial diagnosis [3, 4]. In addition, aGCT patients have a lifetime increased risk for other cancers, primarily estrogen-sensitive cancers (i.e. breast and endometrial cancer) [5, 6]. The molecular landscape of breast and endometrial cancers has been extensively researched, yet no common driver for mutations in breast, endometrial and aGCT has been identified [7]. To our knowledge, there is only one case report examining DNA variants found in women with aGCT and concurrent endometrial cancer [8].

Optimal management of aGCT presents significant challenges. Apart from the tumor stage, no prognostic biomarkers are used for prediction of potential recurrences [9, 10]. There is a lack of evidence-based treatment options for recurrent aGCT, except further surgery, and limited experience with targeted therapy [11–16]. Finally, there is sparse information published about determining a woman’s risk of other cancer diagnoses after an aGCT is identified.

Since the development of high throughput sequencing (Next Generation Sequencing, NGS), studies have described the mutational landscape of aGCT to determine actionable and prognostic variations [17–21]. A missense mutation in FOXL2 (c.402C>G; p.C134W) was reported in ~95% of aGCT [22–24]. However, despite being of value in diagnosing aGCT correctly, a FOXL2 mutation still has limited clinical relevance [25, 26]. Although trunctating KMT2D mutations, TERT promoter mutations and pathogenic TP53 variants have been reported in aGCT-cohorts, a pattern that describes prognostic markers is yet to be identified [17–20, 27–29]. Interestingly, a recent study reported an increased expression of genes with hormone signalling functions in aGCT [30].

Due to the tumour’s rarity, molecular studies on aGCT are naturally limited to a small number of cases or extensive cross-sectional studies. These study designs cannot answer critical questions about the linkage between the genomic landscape and prognostic or actionable targets. To our knowledge, none of the existing molecular variants in aGCT are targetable for personalized treatment. Although several reviews on aGCT exist [31–38], none have systematically mapped the current knowledge of DNA variants in aGCT.

This scoping review aims to systematically describe the DNA variations in aGCT and reference these variants with well-established genetic variant databases. By referencing variations with genetic variant databases, we can report on the variant’s effect on disease development and the potential for targeted therapies.

Methods and design

This review will be conducted in accordance with the methodology outlined by Arksey and O’Malley [39], and amendments proposed by the Joanna Briggs Institute (JBI) [40]. The review protocol is registered at Open Science Framework under this link: https://doi.org/10.17605/OSF.IO/PX4MF. The scoping review will be developed in five stages [39]:

  • Stage 1: Defining the research question.
  • Stage 2: Identification of relevant studies.
  • Stage 3: Selection of the studies.
  • Stage 4: Organisation and tabulation of the data.
  • Stage 5: Summarisation, compilation and documentation of the results.

This protocol was developed in accordance with the guidelines from the PRISMA Extension for Scoping reviews (PRISMA-ScR) checklist [41] (S1 and S2 Checklists).

Stage 1: Identification of the research question

Inspiration for this review was elicited from a recently published scoping review on the molecular alterations in peritoneal mesothelioma (PeM) [42]. This scoping review identified common mutations in rare cancers and used MyCancerGenome.org as the reference for actionable targets or clinical trials [43]. MyCancerGenome.org, OnkoKB, ClinVar, COSMIC, ClinicalTrial.gov are databases that store information about oncogenic mutations, targetable mutations and ongoing clinical trials regarding targeted therapy [43–46]. These databases will also be used as a reference for any molecular alterations identified in this scoping review. This scoping review aims:

  • To explore the DNA alterations associated with aGCT and give an overview of potential treatment possibilities
  • To investigate if reported DNA variations predict risk of recurrence, aggressive disease or a risk of developing other primary malignant tumors
  • To reference molecular alterations found in aGCT with MyCancerGenome.org, OnkoKB, ClinVar, COSMIC, ClinicalTrial.gov (May 2024)
  • To identify knowledge gaps between DNA alterations of aGCT and prognosis potential

Stage 2: Identification of the relevant literature

The authors have developed a set of inclusion criteria based on the ‘Population–Concept–Context (PCC)’ framework proposed by JBI [47].

Search strategy. The search strategy will consist of two search terms (granulosa cell tumour AND molecular alterations). Each element will consist of database-specific subject headings (MeSH), and free text words with relevant truncation and proximity operators. The search terms were inspired by similar search strings published in reviews from the Cochrane Library [16, 48]. An example of the search strategy for Medline (OVID) is presented in Box 1.

The search strategy will be translated for Embase (Ovid), Web of Science and Google Scholar (100-top ranked) and reviewed with an information specialist in health sciences.

Stage 3: Study selection

A summary of the PCC and inclusion and exclusion criteria is shown in Box 2.

Only peer-reviewed original research focusing aGCT and molecular alterations will be included. The aGCT diagnosis must have been defined and validated by pathologists prior to molecular analysis. Only articles describing high throughput sequencing techniques of somatic and germline DNA variations in women with aGCT will be considered. There will be no language or publication date restrictions, and all studies matching our criteria published up until the search date will be considered. Studies with cell lines and targeted DNA sequencing limited to only the FOXL2 variant known to be present in ~95% of aGCT will be excluded. Any reviews of molecular profiles of aGCT and the prognostic values of this information will be used to identify additional primary studies by applying forward and backwards citation searching.

Results will be imported into covidence [49] for screening, and any duplicates will be removed. Two reviewers will screen titles and abstracts, applying inclusion and exclusion criteria (Box 1). Any full-text articles excluded after screening will include the reasoning behind exclusion. A PRISMA flowchart will summarise the search, screening and identification process for relevant studies.Any disagreements will be solved by discussion, or if necessary, an experienced third author will make the final decision.

Screening and study selection will be performed in March 2024.

Stage 4: Charting the data

The authors will use a chart or table (based on the JBI template source of evidence details, characteristics and results extraction instrument) to extract data blinded to each other [47]. Any somatic and germline DNA alterations, known as either pathogenic, likely pathogenic or of unknown significance according to OncoKB Cancer Gene List will be recorded [44]. Data to calculate frequencies will be plotted in STATA Release 17.0 (StataCorp, College Station, TX, USA). Relevant information will be presented in pre-planned tables (see Tables 1, 2 and 3 and Fig 1).

thumbnail
Download:
Fig 1. Suggested table to report gene alterations in >1% of the female adult granulosa cell tumor (aGCT) patients.

N = XX.

https://doi.org/10.1371/journal.pone.0303989.g001

thumbnail
Download:
Table 1. Suggested charting form.

https://doi.org/10.1371/journal.pone.0303989.t001

thumbnail
Download:
Table 2. Pathogenic variants in genes associated with an increased risk of other primary cancers.

https://doi.org/10.1371/journal.pone.0303989.t002

thumbnail
Download:
Table 3. Genes with available targeted therapies.

https://doi.org/10.1371/journal.pone.0303989.t003

Tables 2 and 3 will be generated by referencing any DNA pathogenic and likely pathogenic alterations with established databases (MyCancerGenome.org, OnkoKB, ClinVar, COSMIC, ClinicalTrial.gov) to identify the associated risks of other neoplasms and the possibility of targeted therapies. These proposed tables are preliminary and may be amended as the scoping review progresses.

Stage 5: Collating, summarizing and reporting results

The study’s outcome will be published as a scoping review article containing texts, flow charts and tables. The flow chart will present the search strategy and study selection results. The identification and findings of the selected studies will be elaborated on in the article’s discussion section. Moreover, the research questions will be addressed based on these main findings. Finally, limitations, knowledge gaps and areas requiring further research will be highlighted.

Patient and public involvement

No patient involvement.

Discussion

The proposed scoping review article will systematically map the current knowledge about the DNA alterations in aGCT and the associated clinical impacts of these alterations. Therefore, the focus will be on pathogenic and likely pathogenic variations, as these may impact treatment options and disease development. Only one common missense mutation in FOXL2 (c.402C>G; p.C134W) has been found in ~95% of aGCT [22–24]. Apart from this mutation, reported somatic variants are heterogenous, and little is known about the clinical impact of these variants in aGCT [18, 20]. Collating the results of studies will identify common and recurrent molecular DNA variants describing sub-groups of patients with different risk profiles. This review allows for the comparison of results across publications to identify new common variants. This comparison will assist in identifying knowledge gaps and priorities for clinical trials on actionable variations in aGCT. In addition, any DNA alterations eligible for personalized treatment, including immunotherapy, might be identified by referencing the alteration with well-established databases (MyCancerGenome.org, OnkoKB, ClinVar, COSMIC, ClinicalTrial.gov).

This scoping review methodology was previously used to map the molecular landscape in other rare tumors [42, 50, 51]. Limitations of this scoping-review approach include the broad scope and heterogeneity of studies reviewed. Studies may lack complete mutational data or clinical outcomes such as morbidity and mortality, hampering interpretation. Although NGS encompasses targeted gene-panel sequencing, whole exome and whole genome sequencing, each technique has strengths and limitations. Any conclusions from studies based on different molecular techniques should be cautious in interpretation.

Supporting information

S1 Checklist. PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: Recommended items to address in a systematic review protocol.

https://doi.org/10.1371/journal.pone.0303989.s001

(DOC)

S2 Checklist. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist.

https://doi.org/10.1371/journal.pone.0303989.s002

(DOCX)

References

  1. 1. Schumer ST, Cannistra SA. Granulosa cell tumor of the ovary. J Clin Oncol 2003;21(6):1180–9. pmid:12637488
  2. 2. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136(5):E359–86. pmid:25220842
  3. 3. Sun HD, Lin H, Jao MS, et al. A long-term follow-up study of 176 cases with adult-type ovarian granulosa cell tumors. Gynecol Oncol 2012;124(2):244–9. pmid:22019525
  4. 4. Lee IH, Choi CH, Hong DG, et al. Clinicopathologic characteristics of granulosa cell tumors of the ovary: a multicenter retrospective study. J Gynecol Oncol 2011;22(3):188–95. pmid:21998762
  5. 5. Hammer A, Lauszus FF, Petersen AC. Ovarian granulosa cell tumor and increased risk of breast cancer. Acta obstetricia et gynecologica Scandinavica 2013;92(12):1422–5. pmid:24283356
  6. 6. Nasioudis D, Wilson E, Mastroyannis SA, et al. Increased Risk of Breast and Uterine Cancer Among Women With Ovarian Granulosa Cell Tumors. Anticancer research 2019;39(9):4971–4975. pmid:31519603
  7. 7. Watanabe T, Soeda S, Okoshi C, Fukuda T, Yasuda S, Fujimori K. Landscape of somatic mutated genes and inherited susceptibility genes in gynecological cancer. J Obstet Gynaecol Res 2023;49(11):2629–2643. pmid:37632362
  8. 8. Choi YJ, Ho J, Lee A, et al. Disparate genomic characteristics of concurrent endometrial adenocarcinoma and ovarian granulosa cell tumor, revealed by targeted next-generation sequencing. Pathology, research and practice 2018;214(8):1231–1233. pmid:29937308
  9. 9. Villella J, Herrmann FR, Kaul S, et al. Clinical and pathological predictive factors in women with adult-type granulosa cell tumor of the ovary. Int J Gynecol Pathol 2007;26(2):154–9. pmid:17413982
  10. 10. Miller K, McCluggage WG. Prognostic factors in ovarian adult granulosa cell tumour. J Clin Pathol 2008;61(8):881–4. pmid:18663055
  11. 11. Brown J, Shvartsman HS, Deavers MT, et al. The activity of taxanes compared with bleomycin, etoposide, and cisplatin in the treatment of sex cord-stromal ovarian tumors. Gynecol Oncol 2005;97(2):489–96. pmid:15863149
  12. 12. Burton ER, Brady M, Homesley HD, et al. A phase II study of paclitaxel for the treatment of ovarian stromal tumors: An NRG Oncology/ Gynecologic Oncology Group Study. Gynecol Oncol 2016;140(1):48–52. pmid:26616224
  13. 13. Brown J, Brady WE, Schink J, et al. Efficacy and safety of bevacizumab in recurrent sex cord-stromal ovarian tumors: results of a phase 2 trial of the Gynecologic Oncology Group. Cancer 2014;120(3):344–51. pmid:24166194
  14. 14. Ray-Coquard I, Harter P, Lorusso D, et al. Effect of Weekly Paclitaxel With or Without Bevacizumab on Progression-Free Rate Among Patients With Relapsed Ovarian Sex Cord-Stromal Tumors: The ALIENOR/ENGOT-ov7 Randomized Clinical Trial. JAMA Oncol 2020;6(12):1923–1930. pmid:33030515
  15. 15. How JA, Jazaeri A, Westin SN, et al. The clinical efficacy and safety of single-agent pembrolizumab in patients with recurrent granulosa cell tumors of the ovary: a case series from a phase II basket trial. Invest New Drugs 2021;39(3):829–835. pmid:33415580
  16. 16. Gurumurthy M, Bryant A, Shanbhag S. Effectiveness of different treatment modalities for the management of adult-onset granulosa cell tumours of the ovary (primary and recurrent). Cochrane Database Syst Rev 2014;2014(4):CD006912. pmid:24753008
  17. 17. Pilsworth JA, Cochrane DR, Xia Z, et al. TERT promoter mutation in adult granulosa cell tumor of the ovary. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 2018;31(7):1107–1115. pmid:29449679
  18. 18. Hillman RT, Celestino J, Terranova C, et al. KMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa cell tumors of the ovary. Nature communications 2018;9(1):2496. pmid:29950560
  19. 19. Hillman RT, Lin DI, Lawson B, Gershenson DM. Prevalence of predictive biomarkers in a large cohort of molecularly defined adult-type ovarian granulosa cell tumors. Gynecol Oncol 2021;162(3):728–734. pmid:34238613
  20. 20. Roze J, Monroe G, Kutzera J, et al. Whole Genome Analysis of Ovarian Granulosa Cell Tumors Reveals Tumor Heterogeneity and a High-Grade TP53-Specific Subgroup. Cancers 2020;12(5). pmid:32455687
  21. 21. Roze JF, Kutzera J, Koole W, et al. Familial Occurrence of Adult Granulosa Cell Tumors: Analysis of Whole-Genome Germline Variants. Cancers 2021;13(10). pmid:34069790
  22. 22. Shah SP, Kobel M, Senz J, et al. Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med 2009;360(26):2719–29. pmid:19516027
  23. 23. Takahashi A, Kimura F, Yamanaka A, et al. The FOXL2 mutation (c.402C>G) in adult-type ovarian granulosa cell tumors of three Japanese patients: clinical report and review of the literature. Tohoku J Exp Med 2013;231(4):243–50. pmid:24257635
  24. 24. Jamieson S, Butzow R, Andersson N, et al. The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary. Modern Pathol 2010;23(11):1477–1485. (In English). pmid:20693978
  25. 25. Pilsworth JA, Cochrane DR, Neilson SJ, et al. Adult-type granulosa cell tumor of the ovary: a FOXL2-centric disease. The journal of pathology Clinical research 2021;7(3):243–252. pmid:33428330
  26. 26. Weis-Banke SE, Lerdrup M, Kleine-Kohlbrecher D, et al. Mutant FOXL2C134W Hijacks SMAD4 and SMAD2/3 to Drive Adult Granulosa Cell Tumors. Cancer research 2020;80(17):3466–3479. pmid:32641411
  27. 27. Wang YK, Bashashati A, Anglesio MS, et al. Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes. Nature Genetics 2017;49(6):856–864. pmid:28436987
  28. 28. Hillman RT, Celestino J, Terranova C, et al. KMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa cell tumors of the ovary. Nature Communications 2018;9(1). pmid:29950560
  29. 29. Alexiadis M, Rowley SM, Chu S, et al. Mutational Landscape of Ovarian Adult Granulosa Cell Tumors from Whole Exome and Targeted TERT Promoter Sequencing. Molecular cancer research: MCR 2019;17(1):177–185. pmid:30166312
  30. 30. Khlebus E, Vuttaradhi VK, Welte T, et al. Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors. Molecular cancer research: MCR 2023;21(5):483–494. pmid:37068116
  31. 31. Al Harbi R, McNeish IA, El-Bahrawy M. Ovarian sex cord-stromal tumors: an update on clinical features, molecular changes, and management. Int J Gynecol Cancer 2021;31(2):161–168. pmid:33414107
  32. 32. Schultz KA, Harris AK, Schneider DT, et al. Ovarian Sex Cord-Stromal Tumors. J Oncol Pract 2016;12(10):940–946. pmid:27858560
  33. 33. Young RH. REVIEW: 50TH ANNIVERSARY ISSUE Ovarian sex cord-stromal tumours and their mimics. Pathology 2018;50(1):5–15. pmid:29132723
  34. 34. Hanley KZ, Mosunjac MB. Practical Review of Ovarian Sex Cord–Stromal Tumors. Surgical Pathology Clinics 2019;12(2):587–620. pmid:31097116
  35. 35. Jung D, Almstedt K, Battista MJ, et al. Immunohistochemical markers of prognosis in adult granulosa cell tumors of the ovary ‐ a review. J Ovarian Res 2023;16(1):50. pmid:36869369
  36. 36. Ordulu Z. Update on Ovarian Sex Cord-Stromal Tumors. Clin Lab Med 2023;43(2):245–274. pmid:37169445
  37. 37. Fuller PJ, Leung D, Chu S. Genetics and genomics of ovarian sex cord-stromal tumors. Clin Genet 2017;91(2):285–291. pmid:27813081
  38. 38. Lim D, Oliva E. Ovarian sex cord-stromal tumours: an update in recent molecular advances. Pathology 2018;50(2):178–189. pmid:29275930
  39. 39. Arksey H, O’Malley L. Scoping studies: towards a methodological framework. International journal of social research methodology 2005;8(1):19–32.
  40. 40. Peters MD, Godfrey CM, Khalil H, McInerney P, Parker D, Soares CB. Guidance for conducting systematic scoping reviews. Int J Evid Based Healthc 2015;13(3):141–6. pmid:26134548
  41. 41. Tricco AC, Lillie E, Zarin W, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med 2018;169(7):467–473. pmid:30178033
  42. 42. Dietz MV, van Kooten JP, Paats MS, et al. Molecular alterations and potential actionable mutations in peritoneal mesothelioma: a scoping review of high-throughput sequencing studies. ESMO Open 2023;8(4):101600. pmid:37453150
  43. 43. Holt ME, Mittendorf KF, LeNoue-Newton M, et al. My Cancer Genome: Coevolution of Precision Oncology and a Molecular Oncology Knowledgebase. JCO Clin Cancer Inform 2021;5:995–1004. pmid:34554823
  44. 44. Chakravarty D, Gao J, Phillips SM, et al. OncoKB: A Precision Oncology Knowledge Base. JCO Precis Oncol 2017;2017. pmid:28890946
  45. 45. Landrum MJ, Lee JM, Benson M, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res 2018;46(D1):D1062–D1067. pmid:29165669
  46. 46. Tate JG, Bamford S, Jubb HC, et al. COSMIC: the Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res 2019;47(D1):D941–D947. pmid:30371878
  47. 47. Aromataris E MZE. JBI Manual for Evidence Synthesis. https://synthesismanual.jbi.global.: JBI; 2020.
  48. 48. Brink GJ, Groeneweg JW, Hooft L, Zweemer RP, Witteveen PO. Response to Systemic Therapies in Ovarian Adult Granulosa Cell Tumors: A Literature Review. Cancers (Basel) 2022;14(12). pmid:35740663
  49. 49. Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org.
    • 50. Cotta BH, Choueiri TK, Cieslik M, et al. Current Landscape of Genomic Biomarkers in Clear Cell Renal Cell Carcinoma. Eur Urol 2023;84(2):166–175. pmid:37085424
    • 51. Xie F, Meves A, Lehman JS. The genomic and proteomic landscape in oral lichen planus versus oral squamous cell carcinoma: a scoping review. Int J Dermatol 2022;61(10):1227–1236. pmid:35575880