Discovery of actionable genetic alterations with targeted panel sequencing in children with relapsed or refractory solid tumors
Autoři:
Ji Won Lee aff001; Nayoung K. D. Kim aff002; Soo Hyun Lee aff004; Hee Won Cho aff001; Youngeun Ma aff001; Hee Young Ju aff001; Keon Hee Yoo aff001; Ki Woong Sung aff001; Hong Hoe Koo aff001; Woong-Yang Park aff002
Působiště autorů:
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
aff001; Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
aff002; Geninus Inc., Seoul, Korea
aff003; Department of Translational Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, Texas, United States of America
aff004; Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea
aff005; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
aff006
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0224227
Souhrn
Advances in genomic technologies and the development of targeted therapeutics are making the use of precision medicine increasingly possible. In this study, we explored whether precision medicine can be applied for the management of refractory/relapsed pediatric solid tumors by discovering actionable alterations using targeted panel sequencing. Samples of refractory/relapsed pediatric solid tumors were tested using a targeted sequencing panel covering the exonic DNA sequences of 381 cancer genes and introns across 22 genes to detect clinically significant genomic aberrations in tumors. The molecular targets were tiered from 1 to 5 based on the presence of actionable genetic alterations, strength of supporting evidence, and drug availability in the Republic of Korea. From January 2016 to October 2018, 55 patients were enrolled. The median time from tissue acquisition to drug selection was 29 d (range 14–39), and tumor profiling was successful in 53 (96.4%) patients. A total of 27 actionable alterations in tiers 1–4 were detected in 20 patients (36.4%), and the majority of actionable alterations were copy number variations. The tiers of molecular alterations were tier 1 (clinical evidence) in 4 variants, tier 2 (preclinical evidence) in 8 variants, tier 3 (consensus opinion) in 2 variants, and tier 4 (actionable variants with a drug that is available in other countries but not in the Republic of Korea) in 9 variants. In one patient with relapsed neuroblastoma with ALK F1174L mutation and ALK amplification, lorlatinib was used in a compassionate use program, and it showed some efficacy. In conclusion, using a targeted sequencing panel to discover actionable alterations in relapsed/refractory pediatric solid tumors was practical and feasible.
Klíčová slova:
Human genetics – Pediatrics – Genomic databases – Genomic medicine – Cancer genomics – Gene sequencing – Neuroblastoma – Precision medicine
Zdroje
1. Nageswara Rao AA, Scafidi J, Wells EM, Packer RJ. Biologically targeted therapeutics in pediatric brain tumors. Pediatr Neurol. 2012; 46:203–211. doi: 10.1016/j.pediatrneurol.2012.02.005 22490764
2. Rosell R, Bivona TG, Karachaliou N. Genetics and biomarkers in personalisation of lung cancer treatment. Lancet. 2013; 382:720–731. doi: 10.1016/S0140-6736(13)61715-8 23972815
3. Worst BC, van Tilburg CM, Balasubramanian GP, Fiesel P, Witt R, Freitag A, et al. Next-generation personalised medicine for high-risk paediatric cancer patients—The INFORM pilot study. Eur J Cancer. 2016; 65:91–101. doi: 10.1016/j.ejca.2016.06.009 27479119
4. Harris MH, DuBois SG, Glade Bender JL, Kim A, Crompton BD, Parker E, et al. Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study. JAMA Oncol. 2016
5. Mody RJ, Wu YM, Lonigro RJ, Cao X, Roychowdhury S, Vats P, et al. Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth. JAMA. 2015; 314:913–925. doi: 10.1001/jama.2015.10080 26325560
6. Kline CN, Joseph NM, Grenert JP, van Ziffle J, Talevich E, Onodera C, et al. Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy. Neuro Oncol. 2016
7. Ortiz MV, Kobos R, Walsh M, Slotkin EK, Roberts S, Berger MF, et al. Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center. Pediatr Blood Cancer. 2016; 63:1368–1374. doi: 10.1002/pbc.26002 27082517
8. Chang W, Brohl A, Patidar R, Sindiri S, Shern JF, Wei JS, et al. Multi-Dimensional ClinOmics for Precision Therapy of Children and Adolescent Young Adults with Relapsed and Refractory Cancer: A report from the Center for Cancer Research. Clin Cancer Res. 2016
9. Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics. 2010; 26:589–595. doi: 10.1093/bioinformatics/btp698 20080505
10. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009; 25:2078–2079. doi: 10.1093/bioinformatics/btp352 19505943
11. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010; 20:1297–1303. doi: 10.1101/gr.107524.110 20644199
12. Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013; 31:213–219. doi: 10.1038/nbt.2514 23396013
13. Wilm A, Aw PP, Bertrand D, Yeo GH, Ong SH, Wong CH, et al. LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets. Nucleic Acids Res. 2012; 40:11189–11201. doi: 10.1093/nar/gks918 23066108
14. Ye K, Schulz MH, Long Q, Apweiler R, Ning Z. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics. 2009; 25:2865–2871. doi: 10.1093/bioinformatics/btp394 19561018
15. Shin HT, Choi YL, Yun JW, Kim NKD, Kim SY, Jeon HJ, et al. Prevalence and detection of low-allele-fraction variants in clinical cancer samples. Nat Commun. 2017; 8:1377. doi: 10.1038/s41467-017-01470-y 29123093
16. Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J, Chanthery YH, et al. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013; 3:308–323. doi: 10.1158/2159-8290.CD-12-0418 23430699
17. Kiessling MK, Curioni-Fontecedro A, Samaras P, Lang S, Scharl M, Aguzzi A, et al. Targeting the mTOR Complex by Everolimus in NRAS Mutant Neuroblastoma. PLoS One. 2016; 11:e0147682. doi: 10.1371/journal.pone.0147682 26821351
18. Cen L, Carlson BL, Schroeder MA, Ostrem JL, Kitange GJ, Mladek AC, et al. p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. Neuro Oncol. 2012; 14:870–881. doi: 10.1093/neuonc/nos114 22711607
19. Michaud K, Solomon DA, Oermann E, Kim JS, Zhong WZ, Prados MD, et al. Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts. Cancer Res. 2010; 70:3228–3238. doi: 10.1158/0008-5472.CAN-09-4559 20354191
20. Nakayama R, Zhang YX, Czaplinski JT, Anatone AJ, Sicinska ET, Fletcher JA, et al. Preclinical activity of selinexor, an inhibitor of XPO1, in sarcoma. Oncotarget. 2016; 7:16581–16592. doi: 10.18632/oncotarget.7667 26918731
21. Janku F, Wheler JJ, Naing A, Falchook GS, Hong DS, Stepanek VM, et al. PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res. 2013; 73:276–284. doi: 10.1158/0008-5472.CAN-12-1726 23066039
22. Kansara M, Teng MW, Smyth MJ, Thomas DM. Translational biology of osteosarcoma. Nat Rev Cancer. 2014; 14:722–735. doi: 10.1038/nrc3838 25319867
23. Heldin CH. Targeting the PDGF signaling pathway in tumor treatment. Cell Commun Signal. 2013; 11:97. doi: 10.1186/1478-811X-11-97 24359404
24. Robinson GW, Orr BA, Wu G, Gururangan S, Lin T, Qaddoumi I, et al. Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog-Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032. J Clin Oncol. 2015; 33:2646–2654. doi: 10.1200/JCO.2014.60.1591 26169613
25. Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015; 373:1697–1708. doi: 10.1056/NEJMoa1506859 26510020
26. Rodriguez-Viciana P, Tetsu O, Tidyman WE, Estep AL, Conger BA, Cruz MS, et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science. 2006; 311:1287–1290. doi: 10.1126/science.1124642 16439621
27. del Bufalo F, Carai A, Figa-Talamanca L, Pettorini B, Mallucci C, Giangaspero F, et al. Response of recurrent BRAFV600E mutated ganglioglioma to Vemurafenib as single agent. J Transl Med. 2014; 12:356. doi: 10.1186/s12967-014-0356-1 25524464
28. Tinsley S. To establish the role of mutations in c-KIT tyrosine kinase in the pathogenesis and therapy of core-binding factor-related acute myeloid leukaemia (AML)
29. Infarinato NR, Park JH, Krytska K, Ryles HT, Sano R, Szigety KM, et al. The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Cancer Discov. 2016; 6:96–107. doi: 10.1158/2159-8290.CD-15-1056 26554404
30. Mosse YP, Voss SD, Lim MS, Rolland D, Minard CG, Fox E, et al. Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children′s Oncology Group Study. J Clin Oncol. 2017; 35:3215–3221. doi: 10.1200/JCO.2017.73.4830 28787259
31. George RE, Sanda T, Hanna M, Frohling S, Luther W 2nd, Zhang J, et al. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature. 2008; 455:975–978. doi: 10.1038/nature07397 18923525
32. Mosse YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children′s Oncology Group phase 1 consortium study. Lancet Oncol. 2013; 14:472–480. doi: 10.1016/S1470-2045(13)70095-0 23598171
33. Newman WG, Black GC. Delivery of a clinical genomics service. Genes (Basel). 2014; 5:1001–1017.
34. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013; 499:214–218. doi: 10.1038/nature12213 23770567
35. Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017; 9:34. doi: 10.1186/s13073-017-0424-2 28420421
36. Grobner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K, Rudneva VA, et al. The landscape of genomic alterations across childhood cancers. Nature. 2018; 555:321–327. doi: 10.1038/nature25480 29489754
37. Moreno L, Pearson ADJ, Paoletti X, Jimenez I, Geoerger B, Kearns PR, et al. Early phase clinical trials of anticancer agents in children and adolescents—an ITCC perspective. Nat Rev Clin Oncol. 2017
38. Lee B, Lee JW, Shim JH, Joung JG, Yun JW, Bae JS, et al. Clinical Relevance of Genomic Changes in Recurrent Pediatric Solid Tumors. Transl Oncol. 2018; 11:1390–1397. doi: 10.1016/j.tranon.2018.08.013 30216764
Článok vyšiel v časopise
PLOS One
2019 Číslo 11
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Úspěšná resuscitativní thorakotomie v přednemocniční neodkladné péči
- Dlouhodobá recidiva a komplikace spojené s elektivní operací břišní kýly
Najčítanejšie v tomto čísle
- A daily diary study on maladaptive daydreaming, mind wandering, and sleep disturbances: Examining within-person and between-persons relations
- A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction
- A substitution mutation in a conserved domain of mammalian acetate-dependent acetyl CoA synthetase 2 results in destabilized protein and impaired HIF-2 signaling
- Molecular validation of clinical Pantoea isolates identified by MALDI-TOF