Diverse Oncogenic Fusions and Distinct Gene Expression Patterns Define the Genomic Landscape of Pediatric Papillary Thyroid Carcinoma.

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Abstrakt

Tytuł:: Diverse Oncogenic Fusions and Distinct Gene Expression Patterns Define the Genomic Landscape of Pediatric Papillary Thyroid Carcinoma.
Autorzy:: Stosic A; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.; Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.; Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Fuligni F; Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Anderson ND; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.; Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Davidson S; Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
de Borja R; Genome Informatics, Ontario Institute for Cancer Research, Toronto, Ontario.
Acker M; Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.; Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Forte V; Department of Otolaryngology, Head & Neck Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Otolaryngology, Head & Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
Campisi P; Department of Otolaryngology, Head & Neck Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Otolaryngology, Head & Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
Propst EJ; Department of Otolaryngology, Head & Neck Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Otolaryngology, Head & Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
Wolter NE; Department of Otolaryngology, Head & Neck Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Otolaryngology, Head & Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
Chami R; Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Mete O; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.; Department of Anatomical Pathology, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
Malkin D; Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
Shlien A; Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada. .; Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Wasserman JD; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. .; Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.; Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
Źródło:: Cancer research [Cancer Res] 2021 Nov 15; Vol. 81 (22), pp. 5625-5637. Date of Electronic Publication: 2021 Sep 17.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Baltimore, Md. : American Association for Cancer Research
Original Publication: Chicago [etc.]
MeSH Terms:: Gene Expression Regulation, Neoplastic*
Oncogene Fusion*
Transcriptome*
Biomarkers, Tumor/*genetics
Genomics/*methods
Thyroid Cancer, Papillary/*pathology
Thyroid Neoplasms/*pathology
Adolescent ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Prognosis ; Prospective Studies ; Survival Rate ; Thyroid Cancer, Papillary/genetics ; Thyroid Neoplasms/genetics
References:: Araque DVP, Bleyer A, Brito JP. Thyroid cancer in adolescents and young adults. Future Oncol. 2017;13:1253–61.
Canadian Cancer Statistics 2012. 2012.
Dermody S, Walls A, Harley EH Jr. Pediatric thyroid cancer: An update from the SEER database 2007–2012. Int J Pediatr Otorhinolaryngol. 2016;89:121–6.
Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S, Cerutti JM, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid. 2015;25:716–59.
Hay ID, Johnson TR, Kaggal S, Reinalda MS, Iniguez-Ariza NM, Grant CS, et al. Papillary thyroid carcinoma (PTC) in children and adults: comparison of initial presentation and long-term postoperative outcome in 4432 patients consecutively treated at the mayo clinic during eight decades (1936–2015). World J Surg. 2018;42:329–42.
Hogan AR, Zhuge Y, Perez EA, Koniaris LG, Lew JI, Sola JE. Pediatric thyroid carcinoma: incidence and outcomes in 1753 patients. J Surg Res. 2009;156:167–72.
Alzahrani AS, Alswailem M, Moria Y, Almutairi R, Alotaibi M, Murugan AK, et al. Lung metastasis in pediatric thyroid cancer: radiological pattern, molecular genetics, response to therapy, and outcome. J Clin Endocrinol Metab. 2019;104:103–10.
Rubinstein JC, Herrick-Reynolds K, Dinauer C, Morotti R, Solomon D, Callender GG, et al. Recurrence and complications in pediatric and adolescent papillary thyroid cancer in a high-volume practice. J Surg Res. 2020;249:58–66.
Demidchik YE, Demidchik EP, Reiners C, Biko J, Mine M, Saenko VA, et al. Comprehensive clinical assessment of 740 cases of surgically treated thyroid cancer in children of Belarus. Ann Surg. 2006;243:525–32.
Kumagai A, Namba H, Saenko VA, Ashizawa K, Ohtsuru A, Ito M, et al. Low frequency of BRAF T1796A mutations in childhood thyroid carcinomas. The Journal of Clinical Endocrinol Metabol. 2004;89:4280–4.
Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159:676–90.
Picarsic JL, Buryk MA, Ozolek J, Ranganathan S, Monaco SE, Simons JP, et al. Molecular characterization of sporadic pediatric thyroid carcinoma with the DNA/RNA ThyroSeq v2 next-generation sequencing assay. Pediatr Dev Pathol. 2016;19:115–22.
Prasad ML, Vyas M, Horne MJ, Virk RK, Morotti R, Liu Z, et al. NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States. Cancer. 2016;122:1097–107.
Ricarte-Filho JC, Li S, Garcia-Rendueles ME, Montero-Conde C, Voza F, Knauf JA, et al. Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers. J Clin Invest. 2013;123:4935–44.
Cordioli MI, Moraes L, Bastos AU, Besson P, Alves MT, Delcelo R, et al. Fusion oncogenes are the main genetic events found in sporadic papillary thyroid carcinomas from children. Thyroid. 2017;27:182–8.
Nikita ME, Jiang W, Cheng S-M, Hantash FM, McPhaul MJ, Newbury RO, et al. Mutational analysis in pediatric thyroid cancer and correlations with age, ethnicity, and clinical presentation. Thyroid. 2016;26:227–34.
Sassolas G, Hafdi-Nejjari Z, Ferraro A, Decaussin-Petrucci M, Rousset B, Borson-Chazot F, et al. Oncogenic alterations in papillary thyroid cancers of young patients. Thyroid. 2012;22:17–26.
Alzahrani AS, Alswailem M, Alswailem AA, Al-Hindi H, Goljan E, Alsudairy N, et al. Genetic alterations in pediatric thyroid cancer using a comprehensive childhood cancer gene panel. J Clin Endocrinol Metab. 2020;105:dgaa389.
Bauer AJ. Molecular genetics of thyroid cancer in children and adolescents. Endocrinol Metab Clin North Am. 2017;46:389–403.
Paulson VA, Rudzinski ER, Hawkins DS. Thyroid cancer in the pediatric population. Genes (Basel). 2019;10:723.
Pekova B, Sykorova V, Dvorakova S, Vaclavikova E, Moravcova J, Katra R, et al. RET, NTRK, ALK, BRAF and MET fusions in a large cohort of pediatric papillary thyroid carcinomas. Thyroid. 2020;30:1771–80.
Wasserman JD, Sabbaghian N, Fahiminiya S, Chami R, Mete O, Acker M, et al. DICER1 mutations are frequent in adolescent-onset papillary thyroid carcinoma. J Clin Endocrinol Metab. 2018;103:2009–15.
Osamura R, Grossman A, Korbonits M, Kovacs K, Lopes M, Matsuno A, et al. WHO Classification of Tumours of Endocrine Organs. 2017.
Colebatch AJ, Witkowski T, Waring PM, McArthur GA, Wong SQ, Dobrovic A. Optimizing amplification of the GC-Rich TERT promoter region using 7-Deaza-dGTP for droplet digital PCR quantification of TERT promoter mutations. Clin Chem. 2018;64:745–7.
Anderson ND, de Borja R, Young MD, Fuligni F, Rosic A, Roberts ND, et al. Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors. Science. 2018;361:eaam8419.
Haas BJ, Dobin A, Li B, Stransky N, Pochet N, Regev A. Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods. Genome Biol. 2019;20:213.
Iyer MK, Chinnaiyan AM, Maher CA. ChimeraScan: a tool for identifying chimeric transcription in sequencing data. Bioinformatics. 2011;27:2903–4.
McPherson A, Hormozdiari F, Zayed A, Giuliany R, Ha G, Sun MG, et al. deFuse: an algorithm for gene fusion discovery in tumor RNA-Seq data. PLoS Comput Biol. 2011;7:e1001138.
Nicorici D, Satalan M, Edgren H, Kangaspeska S, Murumagi A, Kallioniemi O, et al. FusionCatcher-a tool for finding somatic fusion genes in paired-end RNA-sequencing data. BioRxiv. 2014;011650.
Wang K, Singh D, Zeng Z, Coleman SJ, Huang Y, Savich GL, et al. MapSplice: accurate mapping of RNA-seq reads for splice junction discovery. Nucleic Acids Res. 2010;38:e178.
The genotype-tissue expression (GTEx) project. Nat Genet. 2013;45:580–5.
Panigrahi P, Jere A, Anamika K. FusionHub: A unified web platform for annotation and visualization of gene fusion events in human cancer. PLoS One. 2018;13:e0196588.
Madhulatha TS. An overview on clustering methods. IOSR Journal of Engineering. 2012;2:719–25.
Yan M, Ye K. Determining the number of clusters using the weighted gap statistic. Biometrics. 2007;63:1031–7.
Anders S, Pyl PT, Huber W. HTSeq–a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:166–9.
Williamson EA, Ince PG, Harrison D, Kendall-Taylor P, Harris PE. G-protein mutations in human pituitary adrenocorticotrophic hormone-secreting adenomas. Eur J Clin Invest. 1995;25:128–31.
Yang J, Gong Y, Yan S, Chen H, Qin S, Gong R. Association between TERT promoter mutations and clinical behaviors in differentiated thyroid carcinoma: a systematic review and meta-analysis. Endocrine. 2020;67:44–57.
Onder S, Sari SO, Yegen G, Sormaz IC, Yilmaz I, Poyrazoglu S, et al. Classic architecture with multicentricity and local recurrence, and absence of TERT promoter mutations are correlates of BRAF (V600E) harboring pediatric papillary thyroid carcinomas. Endocr Pathol. 2016;27:153–61.
Oishi N, Kondo T, Nakazawa T, Mochizuki K, Inoue T, Kasai K, et al. Frequent BRAF (V600E) and absence of TERT promoter mutations characterize sporadic pediatric papillary thyroid carcinomas in japan. Endocr Pathol. 2017;28:103–11.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545–50.
Mostoufi-Moab S, Labourier E, Sullivan L, LiVolsi V, Li Y, Xiao R, et al. Molecular testing for oncogenic gene alterations in pediatric thyroid lesions. Thyroid. 2018;28:60–7.
Galuppini F, Vianello F, Censi S, Barollo S, Bertazza L, Carducci S, et al. Differentiated thyroid carcinoma in pediatric age: Genetic and clinical scenario. Front Endocrinol (Lausanne). 2019;10:552.
Saenko V, Rogounovitch T, Shimizu-Yoshida Y, Abrosimov A, Lushnikov E, Roumiantsev P, et al. Novel tumorigenic rearrangement, Delta rfp/ret, in a papillary thyroid carcinoma from externally irradiated patient. Mutat Res. 2003;527:81–90.
Pietrantonio F, Di Nicolantonio F, Schrock AB, Lee J, Morano F, Fuca G, et al. RET fusions in a small subset of advanced colorectal cancers at risk of being neglected. Ann Oncol. 2018;29:1394–401.
Iyama K, Matsuse M, Mitsutake N, Rogounovitch T, Saenko V, Suzuki K, et al. Identification of Three novel fusion oncogenes, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET, in thyroid cancers of young patients in fukushima. Thyroid. 2017;27:811–8.
Flucke U, van Noesel MM, Wijnen M, Zhang L, Chen CL, Sung YS, et al. TFG-MET fusion in an infantile spindle cell sarcoma with neural features. Genes Chromosomes Cancer. 2017;56:663–7.
Hiemenz MC, Skrypek MM, Cotter JA, Biegel JA. Novel TRIM24-MET fusion in a neonatal brain tumor. JCO Precis Oncol. 2019;1–6.
Panebianco F, Nikitski AV, Nikiforova MN, Kaya C, Yip L, Condello V, et al. Characterization of thyroid cancer driven by known and novel ALK fusions. Endocr Relat Cancer. 2019;26:803–14.
Bastos AU, de Jesus AC, Cerutti JM. ETV6-NTRK3 and STRN-ALK kinase fusions are recurrent events in papillary thyroid cancer of adult population. Eur J Endocrinol. 2018;178:83–91.
Nikitski AV, Rominski SL, Wankhede M, Kelly LM, Panebianco F, Barila G, et al. Mouse model of poorly differentiated thyroid carcinoma driven by STRN-ALK fusion. Am J Pathol. 2018;188:2653–61.
Stratford AL, Boelaert K, Tannahill LA, Kim DS, Warfield A, Eggo MC, et al. Pituitary tumor transforming gene binding factor: a novel transforming gene in thyroid tumorigenesis. J Clin Endocrinol Metab. 2005;90:4341–9.
Read ML, Lewy GD, Fong JC, Sharma N, Seed RI, Smith VE, et al. Proto-oncogene PBF/PTTG1IP regulates thyroid cell growth and represses radioiodide treatment. Cancer Res. 2011;71:6153–64.
Melloni GE, Ogier AG, de Pretis S, Mazzarella L, Pelizzola M, Pelicci PG, et al. DOTS-Finder: a comprehensive tool for assessing driver genes in cancer genomes. Genome Med. 2014;6:44.
Read ML, Fong JC, Modasia B, Fletcher A, Imruetaicharoenchoke W, Thompson RJ, et al. Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage response genes in thyroid cancer. Oncogene. 2017;36:5296–308.
Yoo SK, Lee S, Kim SJ, Jee HG, Kim BA, Cho H, et al. Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers. PLos Genet. 2016;12:e1006239.
Pringle DR, Vasko VV, Yu L, Manchanda PK, Lee AA, Zhang X, et al. Follicular thyroid cancers demonstrate dual activation of PKA and mTOR as modeled by thyroid-specific deletion of Prkar1a and Pten in mice. J Clin Endocrinol Metab. 2014;99:E804–12.
Kari S, Vasko VV, Priya S, Kirschner LS. PKA activates AMPK through LKB1 signaling in follicular thyroid cancer. Front Endocrinol (Lausanne). 2019;10:769.
Cui M, Huang J, Zhang S, Liu Q, Liao Q, Qiu X. Immunoglobulin expression in cancer cells and its critical roles in tumorigenesis. Front Immunol. 2021;12:613530.
Arighi E, Borrello MG, Sariola H. RET tyrosine kinase signaling in development and cancer. Cytokine Growth Factor Rev. 2005;16:441–67.
Hampson S, Stephens D, Wasserman JD. Young age is associated with increased rates of residual and recurrent paediatric differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2018;89:212–8.
Lazar L, Lebenthal Y, Steinmetz A, Yackobovitch-Gavan M, Phillip M. Differentiated thyroid carcinoma in pediatric patients: comparison of presentation and course between pre-pubertal children and adolescents. J Pediatr. 2009;154:708–14.
Chesover AD, Vali R, Hemmati SH, Wasserman JD. Lung metastasis in children with differentiated thyroid cancer: Factors associated with diagnosis and outcomes of therapy. Thyroid. 2020;31:50–60.
Zhang XY, Song HJ, Qiu ZL, Shen CT, Chen XY, Sun ZK, et al. Pulmonary metastases in children and adolescents with papillary thyroid cancer in China: prognostic factors and outcomes from treatment with (131)I. Endocrine. 2018;62:149–58.
Nies M, Vassilopoulou-Sellin R, Bassett RL, Yedururi S, Zafereo ME, Cabanillas ME, et al. Distant metastases from childhood differentiated thyroid carcinoma: clinical course and mutational landscape. J Clin Endocrinol Metab. 2021;106:e1683–e97.
Gertz RJ, Nikiforov Y, Rehrauer W, McDaniel L, Lloyd RV. Mutation in BRAF and other members of the MAPK pathway in papillary thyroid carcinoma in the pediatric population. Arch Pathol Lab Med. 2016;140:134–9.
Substance Nomenclature:: 0 (Biomarkers, Tumor)
Entry Date(s):: Date Created: 20210918 Date Completed: 20220110 Latest Revision: 20220110
Update Code:: 20240105
DOI:: 10.1158/0008-5472.CAN-21-0761
PMID:: 34535459
: Czasopismo naukowe

Pediatric papillary thyroid carcinoma (PPTC) is clinically distinct from adult-onset disease. Although there are higher rates of metastasis and recurrence in PPTC, prognosis remains highly favorable. Molecular characterization of PPTC has been lacking. Historically, only 40% to 50% of childhood papillary thyroid carcinoma (PTC) were known to be driven by genomic variants common to adult PTC; oncogenic drivers in the remainder were unknown. This contrasts with approximately 90% of adult PTC driven by a discrete number of variants. In this study, 52 PPTCs underwent candidate gene testing, followed in a subset by whole-exome and transcriptome sequencing. Within these samples, candidate gene testing identified variants in 31 (60%) tumors, while exome and transcriptome sequencing identified oncogenic variants in 19 of 21 (90%) remaining tumors. The latter were enriched for oncogenic fusions, with 11 nonrecurrent fusion transcripts, including two previously undescribed fusions, STRN-RET and TG-PBF. Most fusions were associated with 3' receptor tyrosine kinase (RTK) moieties: RET, MET, ALK, and NTRK3. For advanced (distally metastatic) tumors, a driver variant was described in 91%. Gene expression analysis defined three clusters that demonstrated distinct expression of genes involved in thyroid differentiation and MAPK signaling. Among RET-CCDC6-driven tumors, gene expression in pediatric tumors was distinguishable from that in adults. Collectively, these results show that the genomic landscape of pediatric PTC is different from adult PTC. Moreover, they identify genomic drivers in 98% of PPTCs, predominantly oncogenic fusion transcripts involving RTKs, with a pronounced impact on gene expression. Notably, most advanced tumors were driven by a variant for which targeted systemic therapy exists. SIGNIFICANCE: This study highlights important distinctions between the genomes and transcriptomes of pediatric and adult papillary thyroid carcinoma, with implications for understanding the biology, diagnosis, and treatment of advanced disease in children.
(©2021 American Association for Cancer Research.)

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