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Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers

Clinical cancer research, 2018-07, Vol.24 (13), p.3059-3068 [Peer Reviewed Journal]

2018 American Association for Cancer Research. ;Copyright American Association for Cancer Research Inc Jul 1, 2018 ;ISSN: 1078-0432 ;EISSN: 1557-3265 ;DOI: 10.1158/1078-0432.ccr-18-0373 ;PMID: 29615459

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Title:
Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers
Author: Pozdeyev, Nikita ; Gay, Laurie M ; Sokol, Ethan S ; Hartmaier, Ryan ; Deaver, Kelsi E ; Davis, Stephanie ; French, Jena D ; Borre, Pierre Vanden ; LaBarbera, Daniel V ; Tan, Aik-Choon ; Schweppe, Rebecca E ; Fishbein, Lauren ; Ross, Jeffrey S ; Haugen, Bryan R ; Bowles, Daniel W
Subjects: Algorithms ; Amplification ; Biological evolution ; Biomarkers, Tumor ; Cancer ; Computational Biology - methods ; Copy number ; Deoxyribonucleic acid ; Diagnostic systems ; DNA ; DNA Mismatch Repair ; DNA repair ; Evolution & development ; Experimental design ; Gene Frequency ; Gene sequencing ; Genes ; Genetic analysis ; Genetic Testing ; Genetic Variation ; Guanosine triphosphatases ; Humans ; Impact analysis ; Janus kinase 2 ; Kinases ; Mismatch repair ; Mutation ; Neoplasm Grading ; Neoplasm Staging ; Oncogenes ; Papillary thyroid cancer ; Pharmacogenomic Variants ; Prognosis ; Promoter Regions, Genetic ; Protein-tyrosine kinase ; Protein-tyrosine kinase receptors ; Rac1 protein ; Thyroid ; Thyroid cancer ; Thyroid Carcinoma, Anaplastic - diagnosis ; Thyroid Carcinoma, Anaplastic - drug therapy ; Thyroid Carcinoma, Anaplastic - genetics ; Transformation ; Tumor Suppressor Proteins - genetics ; Tumors ; Tyrosine
Is Part Of: Clinical cancer research, 2018-07, Vol.24 (13), p.3059-3068
Description: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer (ATC) and identify genetic alterations of potential diagnostic, prognostic, and therapeutic significance. The genetic profiles of 583 advanced differentiated and 196 ATCs generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed. ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared with other thyroid cancer types. DNA mismatch repair deficit and activity of APOBEC cytidine deaminases were identified as mechanisms associated with high mutational burden in a subset of differentiated thyroid cancers and ATCs. Copy number losses and mutations of and , amplification of , amplification of receptor tyrosine kinase genes , and , amplification of immune evasion genes , and , and activating point mutations in small GTPase were associated with ATC. An association of , and amplification with the sensitivity of thyroid cancer cells to lenvatinib was shown Three genetically distinct types of ATCs are proposed. This large-scale analysis describes genetic alterations in a cohort of thyroid cancers enriched in advanced cases. Many novel genetic events previously not seen in thyroid cancer were found. Genetic alterations associated with anaplastic transformation were identified. An updated schematic of thyroid cancer genetic evolution is proposed. .
Publisher: United States: American Association for Cancer Research Inc
Language: English
Identifier: ISSN: 1078-0432
EISSN: 1557-3265
DOI: 10.1158/1078-0432.ccr-18-0373
PMID: 29615459
Source: Geneva Foundation Free Medical Journals at publisher websites
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Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers

2018 American Association for Cancer Research. ;Copyright American Association for Cancer Research Inc Jul 1, 2018 ;ISSN: 1078-0432 ;EISSN: 1557-3265 ;DOI: 10.1158/1078-0432.ccr-18-0373 ;PMID: 29615459

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