Fusion Genes As Biomarkers in Pediatric Cancers: A Review of the Current State and Applicability in Diagnostics and Personalized Therapy

Overview

Journal Cancer Lett

Specialty Oncology

Date 2020 Nov 28

PMID 33248210

Citations 10

Authors

Neetha Nanoth Vellichirammal

Nagendra K Chaturvedi

Shantaram S Joshi

Donald W Coulter

Chittibabu Guda

Affiliations

Soon will be listed here.

Abstract

The incidence of pediatric cancers is rising steadily across the world, along with the challenges in understanding the molecular mechanisms and devising effective therapeutic strategies. Pediatric cancers are presented with diverse molecular characteristics and more distinct subtypes when compared to adult cancers. Recent studies on the genomic landscape of pediatric cancers using next-generation sequencing (NGS) approaches have redefined this field by providing better subtype characterization and novel actionable targets. Since early identification and personalized treatment strategies influence therapeutic outcomes, survival, and quality of life in pediatric cancer patients, the quest for actionable biomarkers is of great value in this field. Fusion genes that are prevalent and recurrent in several pediatric cancers are ideally suited in this context due to their disease-specific occurrence. In this review, we explore the current status of fusion genes in pediatric cancer subtypes and their use as biomarkers for diagnosis and personalized therapy. We discuss the technological advancements made in recent years in NGS sequencing and their impact on fusion detection algorithms that have revolutionized this field. Finally, we also discuss the advantages of pairing liquid biopsy protocols for fusion detection and their eventual use in diagnosis and treatment monitoring.

Citing Articles

A comprehensive overview of liquid biopsy applications in pediatric solid tumors.

Janssen F, Lak N, Janda C, Kester L, Meister M, Merks J NPJ Precis Oncol. 2024; 8(1):172.

PMID: 39097671 PMC: 11297996. DOI: 10.1038/s41698-024-00657-z.

Biological and therapeutic insights from animal modeling of fusion-driven pediatric soft tissue sarcomas.

Kucinski J, Calderon D, Kendall G Dis Model Mech. 2024; 17(6).

PMID: 38916046 PMC: 11225592. DOI: 10.1242/dmm.050704.

Readon: a novel algorithm to identify read-through transcripts with long-read sequencing data.

Chen S, Wang H, Zhang D, Chen R, Luo J Bioinformatics. 2024; 40(6).

PMID: 38808568 PMC: 11162696. DOI: 10.1093/bioinformatics/btae336.

Circulating Cell-Free Tumor Deoxyribonucleic Acid Analysis as a Tool for the Diagnosis and Monitoring of Pediatric Solid Tumors.

Zaninovic L, Baskovic M, Bojanac A, Jezek D Turk Arch Pediatr. 2023; 58(3):241-249.

PMID: 37144257 PMC: 10210601. DOI: 10.5152/TurkArchPediatr.2023.23014.

Molecular genomic landscape of pediatric solid tumors in Chinese patients: implications for clinical significance.

Gong J, Dong L, Wang C, Luo N, Han T, Li M J Cancer Res Clin Oncol. 2023; 149(11):8791-8802.

PMID: 37140698 DOI: 10.1007/s00432-023-04756-5.

References

Heyer E, Deveson I, Wooi D, Selinger C, Lyons R, Hayes V . Diagnosis of fusion genes using targeted RNA sequencing. Nat Commun. 2019; 10(1):1388. PMC: 6437215. DOI: 10.1038/s41467-019-09374-9. View

Dinh T, Vitucci E, Wauthier E, Graham R, Pitman W, Oikawa T . Comprehensive analysis of The Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma. Sci Rep. 2017; 7:44653. PMC: 5356346. DOI: 10.1038/srep44653. View

Gao Q, Liang W, Foltz S, Mutharasu G, Jayasinghe R, Cao S . Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. Cell Rep. 2018; 23(1):227-238.e3. PMC: 5916809. DOI: 10.1016/j.celrep.2018.03.050. View

Stahl M, Ranft A, Paulussen M, Bolling T, Vieth V, Bielack S . Risk of recurrence and survival after relapse in patients with Ewing sarcoma. Pediatr Blood Cancer. 2011; 57(4):549-53. DOI: 10.1002/pbc.23040. View

Lawrence M, Stojanov P, Polak P, Kryukov G, Cibulskis K, Sivachenko A . Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013; 499(7457):214-218. PMC: 3919509. DOI: 10.1038/nature12213. View

Fischer M, Schwieger M, Horn S, Niebuhr B, Ford A, Roscher S . Defining the oncogenic function of the TEL/AML1 (ETV6/RUNX1) fusion protein in a mouse model. Oncogene. 2005; 24(51):7579-91. DOI: 10.1038/sj.onc.1208931. View

Sandberg A, Bridge J . Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet. 2003; 145(1):1-30. View

Zoubek A, Dockhorn-Dworniczak B, Delattre O, Christiansen H, Niggli F, Smith T . Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients?. J Clin Oncol. 1996; 14(4):1245-51. DOI: 10.1200/JCO.1996.14.4.1245. View

Jia Y, Xie Z, Li H . Intergenically Spliced Chimeric RNAs in Cancer. Trends Cancer. 2017; 2(9):475-484. PMC: 5305119. DOI: 10.1016/j.trecan.2016.07.006. View

10.

Usami I, Imamura T, Takahashi Y, Suenobu S, Hasegawa D, Hashii Y . Discontinuation of L-asparaginase and poor response to prednisolone are associated with poor outcome of ETV6-RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia. Int J Hematol. 2019; 109(4):477-482. DOI: 10.1007/s12185-019-02599-w. View

11.

CASPERSSON T, LOMAKKA G, ZECH L . The 24 fluorescence patterns of the human metaphase chromosomes - distinguishing characters and variability. Hereditas. 1972; 67(1):89-102. DOI: 10.1111/j.1601-5223.1971.tb02363.x. View

12.

Peter M, Couturier J, Pacquement H, Michon J, Thomas G, Magdelenat H . A new member of the ETS family fused to EWS in Ewing tumors. Oncogene. 1997; 14(10):1159-64. DOI: 10.1038/sj.onc.1200933. View

13.

Zill O, Banks K, Fairclough S, Mortimer S, Vowles J, Mokhtari R . The Landscape of Actionable Genomic Alterations in Cell-Free Circulating Tumor DNA from 21,807 Advanced Cancer Patients. Clin Cancer Res. 2018; 24(15):3528-3538. DOI: 10.1158/1078-0432.CCR-17-3837. View

14.

Ferreira E, Barros B, de Souza J, Almeida R, Torrezan G, Garcia S . A genomic case study of desmoplastic small round cell tumor: comprehensive analysis reveals insights into potential therapeutic targets and development of a monitoring tool for a rare and aggressive disease. Hum Genomics. 2016; 10(1):36. PMC: 5116179. DOI: 10.1186/s40246-016-0092-0. View

15.

Bhakta N, Liu Q, Ness K, Baassiri M, Eissa H, Yeo F . The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE). Lancet. 2017; 390(10112):2569-2582. PMC: 5798235. DOI: 10.1016/S0140-6736(17)31610-0. View

16.

Smoll N, Drummond K . The incidence of medulloblastomas and primitive neurectodermal tumours in adults and children. J Clin Neurosci. 2012; 19(11):1541-4. DOI: 10.1016/j.jocn.2012.04.009. View

17.

Mitelman F, Johansson B, Mertens F . Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Nat Genet. 2004; 36(4):331-4. DOI: 10.1038/ng1335. View

18.

Klega K, Imamovic-Tuco A, Ha G, Clapp A, Meyer S, Ward A . Detection of Somatic Structural Variants Enables Quantification and Characterization of Circulating Tumor DNA in Children With Solid Tumors. JCO Precis Oncol. 2018; 2018. PMC: 6049092. DOI: 10.1200/PO.17.00285. View

19.

Mullighan C, Miller C, Radtke I, Phillips L, Dalton J, Ma J . BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature. 2008; 453(7191):110-4. DOI: 10.1038/nature06866. View

20.

Dawson S, Tsui D, Murtaza M, Biggs H, Rueda O, Chin S . Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013; 368(13):1199-209. DOI: 10.1056/NEJMoa1213261. View