Research
Our lab works on the clinical and molecular aspects of solid tumours of childhood, particularly germ cell tumours (GCTs) – of which testicular cancer is the most common form. Our work has established emphasis on the role of non-coding RNAs such as microRNAs, which are short, non-protein-coding RNAs that regulate gene expression post-transcriptionally and are aberrantly expressed in cancer. We demonstrated for the first time that the miR-371~373 and miR-302/367 clusters are highly over-expressed in all malignant GCTs, regardless of patient age, histological subtype or anatomical site (published in Cancer Research in 2010). This is a specific change, as these microRNAs are not co-ordinately dysregulated in any other malignancy or disease state. We subsequently were the first to demonstrate the potential utility of specific circulating microRNAs for diagnosis, disease-monitoring and detection of relapse in GCTs as well as other childhood tumours.
Our current research has four main overarching themes:
1) Exploring clonal dynamics of germ cell tumours
We are undertaking comprehensive molecular profiling of germ cell tumours, to uncover their spatio-temporal relationship and phylogeny. This work will facilitate our understanding of the mechanisms of cisplatin sensitivity and resistance.
2) Role of the tumour microenvironment in testicular germ cell tumours
This work includes an exploration of the role of tumour-derived extracellular vesicles and their cargo on cells of the tumour microenvironment.
3) Novel therapeutic approaches in malignant germ cell tumours
Having investigated the effects of restoring levels of under-expressed microRNAs in malignant GCTs, highlighting the importance of the LIN28/let-7 axis (published in Cancer Research), we are now exploring the potential of replenishing other putative tumour-suppressor microRNAs, as well as investigating the consequences of targeting over-expressed microRNAs.
4) Improving diagnostic and disease-monitoring approaches for cancer, including germ cell tumours
Following demonstration that levels of microRNAs from the miR-371~373 and miR-302/367 clusters are elevated in the serum at malignant GCT diagnosis, may be tracked during treatment and are sensitive for relapse detection (published in American Journal of Clinical Pathology, Nature Reviews Urology and British Journal of Cancer), we now have serum microRNA outcomes embedded in prospective international clinical trials and are developing the assay for clinical use. We are also identifying serum microRNAs that can be used for risk-stratification and prognosis. We have also highlighted the potential clinical utility of circulating microRNA profiles in other solid tumours of childhood, including high-risk MYCN-amplified neuroblastoma.
Publications
Key publications (since 2021 only) C = corresponding author
1. Diezi M, Pizer B, Murray MJ C, on behalf of the SIOPE Brain Tumour Group Central Nervous System Germ Cell Tumour Subgroup. Overview of current European practice for the management of patients with intracranial germ cell tumours. European Journal of Cancer Paediatric Oncology, 2024, In Press, https://www.ejcped.com/article/S2772-610X(24)00005-9/fulltext
2. Pashankar F*, Murray MJ* C , Gell J, Macdonald N, Shamash J, Klosterkemper L, Olson T, Hirsch M, Lockley M, Sara Stoneham S, Frazier AL. Consensus and controversy in the management of pediatric and adult patients with ovarian immature teratoma: the Malignant Germ Cell International Consortium perspective. *joint first authors. eClinicalMedicine, 2024, In Press, Published: February 06, 2024. DOI: https://doi.org/10.1016/j.eclinm.2024.102453
3. Alonso-Crisostomo L, Trendell J, Ferraresso M, Bailey S, Ward D, Scurlock ZGL, Wenlock SC, Bastos CAP, Jugdaohsingh R, Faria NJ, Enright AJ, Scarpini CG, Coleman N, Murray MJC Testicular germ cell tumour cells release microRNA-containing extracellular vesicles that induce phenotypic and genotypic changes in cells of the tumour microenvironment. International Journal of Cancer, 2024 Jan 15;154(2):372-388. doi: 10.1002/ijc.34697. Epub 2023 Aug 26.
4. Green R, Ahmed A, Fleming B, Long A-M, Behjati B, Trotman J, Tarpey P, Nicholson JC, Coleman N, Hook CE, Murray MJC. Wilms tumor with raised serum alpha-fetoprotein – highlighting the need for novel circulating biomarkers. Pediatric Developmental Pathology, 2023 Dec 14:10935266231213467. doi: 10.1177/10935266231213467. Online ahead of print.
5. Bailey S, Ferraresso MF, Alonso-Crisostomo L, Ward D, Smith S, Nicholson JC, Saini HK, Enright AJ, Scarpini CG, Coleman N, Murray MJC. Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption. British Journal of Cancer, 2023 Oct;129(9):1451-1461. doi: 10.1038/s41416-023-02453-1. Epub 2023 Oct 3.
6. Lafin JT, Scarpini CG, Amini A, Konneh B, Howard JM, Gerald T, Nuno M, Piao J, Savelyeva A, Wang Z, Jeffrey Gagan, Jia L, Lewis CM, Murray S, Sawa YC, Margulis V, Woldu SL, Strand DW, Coleman N, Amatruda JF, Frazier AL, Murray MJ, Bagrodia A. Refining the serum miR-371a-3p test for viable germ cell tumor detection: identification and definition of an indeterminate range. Scientific Reports, 2023, June 29;13(1):10558. doi: 10.1038/s41598-023-37271-1.
7. Prokoph N, Matthews JD, Trigg RM, Montes-Mojarro IA, Burke GAA, Fend F, Merkel O, Kenner L, Georger B, Johnston R, Murray MJ, Rigaud C, Brugières L, Turner S. Patient-derived xenograft models of ALK+ ALCL reveal preclinical promise for therapy with Brigatinib. British Journal of Haematology, 2023 Sep;202(5):985-994. doi: 10.1111/bjh.18953. Epub 2023 Jun 25.
8. Murray MJC, Scarpini CG, Coleman N. Serum tumour markers for testicular cancer recurrence. Nature Reviews Urology, 2023 Aug;20(8):459-460. doi: 10.1038/s41585-023-00782-7.
9. Santarosa Vieira AG, Vidya Puthenpura V, Krailo M, Fallahazad N, Brougham M, Murray MJ, Frazier AL, Lopes LF, Pashankar F. Adjuvant chemotherapy does not improve outcome in children with ovarian immature teratoma: a comparative analysis of clinical trial data from the Malignant Germ Cell International Consortium. Pediatric Blood & Cancer, 2023 Aug;70(8):e30426. doi: 10.1002/pbc.30426. Epub 2023 May 26.
10. Chadda KR, Solano-Paez P, Khan S, Phyu P, Horan G, Trotman J, Tarpey P, Erker C, Lindsay H, Addy D, Jacques T, Allinson K, Pizer B, Huang A, Murray MJC. Embryonal Tumor with Multilayered Rosettes (ETMR): implications for diagnosis and therapy. NeuroOncology Advances, 2023 Apr 26;5(1):vdad052. doi: 10.1093/noajnl/vdad052. eCollection 2023 Jan-Dec.
11. Laidlaw S, Crisostomo LA, Bailey S, Saini HK, Molnár A, Nicholson JC, Enright AJ, Scarpini CG, Rahbari R, Coleman N, Murray MJC. Small non-coding RNA sequencing reveals global dysregulation of piwi-interacting RNAs (piRNAs) in gonadal malignant germ cell tumours. Andrology, 2023 May;11(4):738-755. doi: 10.1111/andr.13312. Epub 2022 Oct 26.
12. Konneh B, Lafin JT, Howard J, Gerald T, Amini A, Savelyeva A, Woldu SL, Lewis CM, Jia L, Margulis V, Coleman N, Scarpini CG, Frazier AL, Murray MJ, Amatruda JF, Bagrodia A. Evaluation of serum miR-371a-3p to predict viable germ cell tumor in patients with pure seminoma receiving retroperitoneal lymph node dissection. Andrology, 2023 May;11(4):634-640. doi: 10.1111/andr.13317. Epub 2022 Nov 2.
13. De Noon S, Piggott R, Trotman J, Tadross J, Fittall M, Hongtao Ye H, Murray MJ, Coleman N, Watkins J, Hubank M, Tarpey P, Behjati S, Flanagan AM. Recurrent FOSL1 rearrangements in desmoplastic fibroblastoma. The Journal of Pathology, 2023 Feb;259(2):119-124. doi: 10.1002/path.6038. Epub 2023 Jan 3.
14. Briggs M, Das A, Firth H, Levine A, Ramirez SS, Negm L, Ercan AB, Chung J, Bianchi V, Jalloh I, Phyu P, Thorp N, Grundy R, Hawkins C, Trotman J, Tarpey P, Tabori U, Allinson K, Murray MJC. Recurrent posterior fossa Group A (PFA) ependymoma in a young child with constitutional mismatch repair deficiency (CMMRD). Neuropathology and Applied Neurobiology, 2023 Feb;49(1):e12862. doi: 10.1111/nan.12862. Epub 2022 Nov 18.
15. Fonseca A, Lobo J, Hazard FKG, Gell J, Nicholls P, Weiss R, Klosterkemper L, Volchenboum S, James C. Nicholson JC, Frazier AL, Amatruda JF, Bagrodia A, Lockley M, Murray MJC. Advancing clinical and translational research in germ cell tumours (GCT): recommendations from the Malignant Germ Cell International Consortium. British Journal of Cancer, 2022 Nov;127(9):1577-1583. doi: 10.1038/s41416-022-02000-4. Epub 2022 Oct 13.
16. Chadda KR, Blakey EE, Coleman N, Murray MJC. The clinical utility of dysregulated microRNA expression in paediatric solid tumours. European Journal of Cancer, 2022 Nov;176:133-154. doi: 10.1016/j.ejca.2022.09.010. Epub 2022 Oct 7.
17. Fankauser CD, Nuño M, Murray MJ, Frazier AL, Bagrodia A. Circulating microRNAs for detecting germ cell tumours: a narrative review. European Urology Focus, 2022 May;8(3):660-662. doi: 10.1016/j.euf.2022.04.008. Epub 2022 May 7.
18. Oliver TRW, Chappell L, Sanghvi R, Deighton L, Ansari-Pour N, Dentro SC, Neville M, Young MD, Coorens THH, Jung H, Butler T, Leongamornlet D, Sanders M, Hooks Y, Cagan A, Mitchell TJ, Cortes-Ciriano I, Warren AY, Wedge D, Heer R, Coleman N, Murray MJ, Campbell PJ, Rahbari R, Behjati S. Clonal diversification and histogenesis of malignant germ cell tumours. Nature Communications, 2022 Aug 11;13(1):4272. doi: 10.1038/s41467-022-31375-4.
19. Fonseca A, Faure-Conter C, Murray MJ, Fangusaro J, Bailey S, Goldman S, Khatua S, Frappaz D, Calaminus G, Dhall G, Nicholson JC, Bouffet E, Bartels U. Pattern of treatment failures in patients with central nervous system non-germinomatous germ cell tumors (CNS-NGGCT): A
pooled analysis of clinical trials. NeuroOncology. 2022 Nov 2;24(11):1950-1961. doi: 10.1093/neuonc/noac057.
20. Murray MJC, Hall NJ, Stoneham S, Penn A, Brougham M, Nicholson JC. Comment on: Standardizing the surgical management of benign ovarian tumors in children and adolescents: A best practice Delphi consensus statement. Pediatric Blood & Cancer. 2022 Nov;69(11):e29690. doi: 10.1002/pbc.29690. Epub 2022 Apr 4.
21. Morana G*, Shaw D*, MacDonald SM, Alapetite C, Ajithkumar T, Bhatia A, Brisse H, Jaimes C, Czech T, Dhall G, Fangusaro J, Faure-Conter C, Fouladi M, Hargrave D, Harreld J, Mitra D, Nicholson JC, Souweidane M, Timmermann B, Calaminus G, Bartels U, Bison B, Murray MJC. Imaging response assessment for Central Nervous System Germ Cell Tumours: consensus recommendations from the European Society for Paediatric Oncology Brain Tumour Group and North American Children’s Oncology Group. Lancet Oncology, 2022, May;23(5):e218-e228. doi: 10.1016/S1470-2045(22)00063-8.
22. Trotman J, Armstrong A, Firth H, Trayers C, Watkins J, Allinson K, Jacques TS, Nicholson JC, Burke GAA, Sam Behjati S*, Murray MJ*C, Hook CE*, Tarpey P*, on behalf of Genomics England Research Consortium. The NHS England 100,000 Genomes Project – Feasibility and utility of centralised genome sequencing for children with cancer. British Journal Cancer, 2022 Jul;127(1):137-144. doi: 10.1038/s41416-022-01788-5. Epub 2022 Apr 22. *Joint senior and co-corresponding authors.
23. Frappaz D, Dhall G, Murray MJ, Goldman S, Faure-Conter C, Allen J, Kortmann R, Haas-Kogen D, Morana G, Finlay J, Nicholson JC, Bartels U, Souweidane M, Schoenberger S, Vasiljevic A, Robertson P, Albanese A, Alapetite C, Czech T, Lassman A, Lau C, Wen PY, Schiff D, Shaw D, Calaminus G, Bouffet E. Intracranial germ cell tumors in Adolescents and Young Adults: European and North American consensus review, current management and future development. NeuroOncology, 2022 Apr 1;24(4):516-527. doi: 10.1093/neuonc/noab252.
24. Murray MJC, Moleron R, Adamski J, English M, Burke GAA, Cross J, Ajithkumar T, Stoneham S, Nicholson JC. Vinblastine monotherapy induction prior to radiotherapy for patients with intracranial germinoma during the COVID-19 pandemic. Pediatric Blood & Cancer, 2022 Jan;69(1):e29359. doi: 10.1002/pbc.29359. Epub 2021 Sep 14.
25. Piao J, Lafin L, Scarpini CG, Nuno M, Syring I, Dieckmann KP, Belge G, Ellinger J, Amatruda JF, Bagrodia A, Krailo MD, Coleman N, Frazier AL, Murray MJC. A multi-institutional pooled analysis demonstrates the utility of circulating miR-371a-3p alone for testicular malignant germ cell tumour diagnosis. Clinical Genitourinary Cancer, 2021 Dec;19(6):469-479. doi: 10.1016/j.clgc.2021.08.006. Epub 2021 Sep 15.
26. Skowron MA, Oing C, Bremmer F, Ströbel P, Bokemeyer C, Murray MJ, Coleman N, Amatruda JF, Honecker F, Albers P, Nettersheim D. The developmental origin of cancers defines basic principles of cisplatin resistance. Cancer Letters, 2021 Oct 28;519:199-210. doi: 10.1016/j.canlet.2021.07.037. Epub 2021 Jul 25.
27. Leão R, Albersen M, Looijenga LHJ, Tandstad T, Kollmansberger C, Murray MJ, Culine S, Coleman N, Belge G, Hamilton RJ, Dieckmann K-P. Circulating microRNAs - The next generation serum biomarkers in testicular germ cell tumours: A systematic review. European Urology, 2021 Oct;80(4):456-466. doi: 10.1016/j.eururo.2021.06.006. Epub 2021 Jun 24.
28. Lafin JT, Murray MJ, Coleman N, Frazier AL, Amatruda JF, Bagrodia A. The road ahead for circulating microRNAs in diagnosis and management of testicular germ cell tumors. Molecular Diagnosis & Therapy, 2021;25:269-271.
29. Lafin JT, Kenigsberg A, Meng X, Abe D, Savalyeva A, Singla N, Woldu SL, Lotan Y, Mauck R, Lewis C, Margulis V, Wong D, Jia L, Kapur P, Xu L, Frazier AL, Strand D, Coleman N, Murray MJ, Amatruda JF, Bagrodia A. Serum small RNA sequencing and miR-375 assay do not identify the presence of pure teratoma at post-chemotherapy retroperitoneal lymph node dissection. European Urology Open Science, 2021;26:83-87.
30. Fern LA, Greenwood M, Smith S, Brand S, Coleman N, Stark DP, Murray MJ. Pre-implementation assessment of the acceptability of using circulating microRNAs for follow-up of malignant germ-cell-tumours. Clinical Genitourinary Cancer, 2021 Oct;19(5):381-387. doi: 10.1016/j.clgc.2021.03.005. Epub 2021 Mar 17.
31. Coorens THH, Collord G, Lu W, Mitchell E, Ijaz J, Roberts T, Oliver TRW, Burke GA, Gattens M, Dickens E, Nangalia J, Tischkowitz M, Anderson J, Shlien A, Godfrey A, Murray MJ*, Behjati S*. Clonal hematopoiesis and therapy-related myeloid neoplasms following neuroblastoma treatment. *Joint senior authors. Blood, 2021 May 27;137(21):2992-2997. doi: 10.1182/blood.2020010150.
32. Chadda KR, Holland K, Scoffings D, Dean A, Jacques TS, Trotman J, Tarpey P, Allinson A, Murray MJC, on behalf of Genomics England Research Consortium. A rare case of paediatric astroblastoma with concomitant MN1-GTSE1 and EWSR1-PATZ1 gene fusions altering management. Neuropathology and Applied Neurobiology, 2021 Oct;47(6):882-888. doi: 10.1111/nan.12701. Epub 2021 Feb 22.
33. Ci B, Lin S-Y, Yao B, Luo D, Xu L, Krailo M, Murray M, Amatruda J, Frazier A, Xie Y. Developing and using a data commons for understanding the molecular characteristics of germ cell tumors. Protocol Chapter. Editor: Aditya Bagrodia and James Amatruda. Title: Testicular Germ Cell Tumors. Methods in Molecular Biology, 2021; 2195:263-275. ISBN 978-1-07-160860-9.
34. Murray MJC, Scarpini CG, Coleman N. A circulating microRNA panel for malignant germ cell tumor diagnosis and monitoring. Protocol Chapter. Editor: Aditya Bagrodia and James Amatruda. Title: Testicular Germ Cell Tumors. Methods in Molecular Biology, 2021;2195:225-243. doi: 10.1007/978-1-0716-0860-9_15.
35. Murray MJC, Smith S, Ward D, Verduci L, Nicholson JC, Scarpini CG, Coleman N. Circulating microRNAs as biomarkers to assist the management of the malignant germ cell tumour subtype choriocarcinoma. Translational Oncology, 2021;14:100904.
36. Badia RR, Abe D, Wong D, Singla N, Savelyeva A, Chertack N, Woldu SL, Lotan Y, Mauck R, Ouyang D, Meng X, Lewis CM, Majmudar K, Jia L, Kapur P, Xu L, Frazier AL, Margulis V, Strand DW, Coleman N, Murray MJ, Amatruda JF, Lafin JT, Bagrodia A. Real-world application of pre-orchiectomy miR-371a-3p test in testicular germ cell tumor management. Journal of Urology, 2021;205:137-144.
37. Shaikh F, Stark D, Fonseca A, Dang H, Xia C, Krailo M, Pashankar F, Rodriguez-Galindo C, Olson TA, Nicholson JC, Murray MJ, Amatruda JF, Billmire D, Stoneham S, Frazier AL. Outcomes of adolescent males with extracranial metastatic germ cell tumors: a report from the Malignant
Germ Cell Tumor International Consortium. Cancer, 2021 Jan 15;127(2):193-202. doi: 10.1002/cncr.33273. Epub 2020 Oct 20.
38. Bagrodia A, Savelyeva A, Lafin JT, Speir RW, Chesnut GT, Frazier AL, Woldu SL, Margulis V, Murray MJ, Amatruda JF, Lotan Y. Impact of Circulating microRNA test (miRNA-371a-3p) on Appropriateness of Treatment and Cost Outcomes in Patients with Stage I Nonseminomatous Germ Cell Tumors. BJU International, 2021 Jul;128(1):57-64. doi: 10.1111/bju.15288.
