Major Oncogenic Drivers and Their Clinicopathological Correlations in Sporadic Childhood Papillary Thyroid Carcinoma in Belarus
Childhood papillary thyroid carcinoma (PTC) diagnosed after the Chernobyl accident in Belarus displayed a high frequency of gene rearrangements and low frequency of point mutations. Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have...
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| Veröffentlicht in: | Cancers 2021-07, Vol.13 (13), p.3374 |
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| creator | Rogounovitch, Tatiana I. Mankovskaya, Svetlana V. Fridman, Mikhail V. Leonova, Tatiana A. Kondratovitch, Victor A. Konoplya, Natalya E. Yamashita, Shunichi Mitsutake, Norisato Saenko, Vladimir A. |
| description | Childhood papillary thyroid carcinoma (PTC) diagnosed after the Chernobyl accident in Belarus displayed a high frequency of gene rearrangements and low frequency of point mutations. Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have not been reported. Here, we determine the major oncogenic events in PTC from non-exposed Belarusian children and assess their clinicopathological correlations. Among the 34 tumors, 23 (67.6%) harbored one of the mutually exclusive oncogenes: 5 (14.7%) BRAFV600E, 4 (11.8%) RET/PTC1, 6 (17.6%) RET/PTC3, 2 (5.9%) rare fusion genes, and 6 (17.6%) ETV6ex4/NTRK3. No mutations in codons 12, 13, and 61 of K-, N- and H-RAS, BRAFK601E, or ETV6ex5/NTRK3 or AKAP9/BRAF were detected. Fusion genes were significantly more frequent than BRAFV600E (p = 0.002). Clinicopathologically, RET/PTC3 was associated with solid growth pattern and higher tumor aggressiveness, BRAFV600E and RET/PTC1 with classic papillary morphology and mild clinical phenotype, and ETV6ex4/NTRK3 with follicular-patterned PTC and reduced aggressiveness. The spectrum of driver mutations in sporadic childhood PTC in Belarus largely parallels that in Chernobyl PTC, yet the frequencies of some oncogenes may likely differ from those in the early-onset Chernobyl PTC; clinicopathological features correlate with the oncogene type. |
| doi_str_mv | 10.3390/cancers13133374 |
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Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have not been reported. Here, we determine the major oncogenic events in PTC from non-exposed Belarusian children and assess their clinicopathological correlations. Among the 34 tumors, 23 (67.6%) harbored one of the mutually exclusive oncogenes: 5 (14.7%) BRAFV600E, 4 (11.8%) RET/PTC1, 6 (17.6%) RET/PTC3, 2 (5.9%) rare fusion genes, and 6 (17.6%) ETV6ex4/NTRK3. No mutations in codons 12, 13, and 61 of K-, N- and H-RAS, BRAFK601E, or ETV6ex5/NTRK3 or AKAP9/BRAF were detected. Fusion genes were significantly more frequent than BRAFV600E (p = 0.002). Clinicopathologically, RET/PTC3 was associated with solid growth pattern and higher tumor aggressiveness, BRAFV600E and RET/PTC1 with classic papillary morphology and mild clinical phenotype, and ETV6ex4/NTRK3 with follicular-patterned PTC and reduced aggressiveness. The spectrum of driver mutations in sporadic childhood PTC in Belarus largely parallels that in Chernobyl PTC, yet the frequencies of some oncogenes may likely differ from those in the early-onset Chernobyl PTC; clinicopathological features correlate with the oncogene type.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13133374</identifier><identifier>PMID: 34282777</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Age ; Children ; Children & youth ; Chromosomes ; Codons ; Families & family life ; Genes ; Girls ; Growth patterns ; H-Ras protein ; Kinases ; Lymphatic system ; Metastasis ; Morphology ; Multivariate analysis ; Mutation ; Papillary thyroid carcinoma ; Phenotypes ; Radiation ; Ret protein ; Thyroid cancer ; Tumors ; Ultrasonic imaging</subject><ispartof>Cancers, 2021-07, Vol.13 (13), p.3374</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-9cbb2767a232991755067f937b8f88c938f633f480794d588145d6a5b1af5ec13</citedby><cites>FETCH-LOGICAL-c442t-9cbb2767a232991755067f937b8f88c938f633f480794d588145d6a5b1af5ec13</cites><orcidid>0000-0003-2844-3121 ; 0000-0002-2744-8046</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268670/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268670/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27915,27916,53782,53784</link.rule.ids></links><search><creatorcontrib>Rogounovitch, Tatiana I.</creatorcontrib><creatorcontrib>Mankovskaya, Svetlana V.</creatorcontrib><creatorcontrib>Fridman, Mikhail V.</creatorcontrib><creatorcontrib>Leonova, Tatiana A.</creatorcontrib><creatorcontrib>Kondratovitch, Victor A.</creatorcontrib><creatorcontrib>Konoplya, Natalya E.</creatorcontrib><creatorcontrib>Yamashita, Shunichi</creatorcontrib><creatorcontrib>Mitsutake, Norisato</creatorcontrib><creatorcontrib>Saenko, Vladimir A.</creatorcontrib><title>Major Oncogenic Drivers and Their Clinicopathological Correlations in Sporadic Childhood Papillary Thyroid Carcinoma in Belarus</title><title>Cancers</title><description>Childhood papillary thyroid carcinoma (PTC) diagnosed after the Chernobyl accident in Belarus displayed a high frequency of gene rearrangements and low frequency of point mutations. Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have not been reported. Here, we determine the major oncogenic events in PTC from non-exposed Belarusian children and assess their clinicopathological correlations. Among the 34 tumors, 23 (67.6%) harbored one of the mutually exclusive oncogenes: 5 (14.7%) BRAFV600E, 4 (11.8%) RET/PTC1, 6 (17.6%) RET/PTC3, 2 (5.9%) rare fusion genes, and 6 (17.6%) ETV6ex4/NTRK3. No mutations in codons 12, 13, and 61 of K-, N- and H-RAS, BRAFK601E, or ETV6ex5/NTRK3 or AKAP9/BRAF were detected. Fusion genes were significantly more frequent than BRAFV600E (p = 0.002). Clinicopathologically, RET/PTC3 was associated with solid growth pattern and higher tumor aggressiveness, BRAFV600E and RET/PTC1 with classic papillary morphology and mild clinical phenotype, and ETV6ex4/NTRK3 with follicular-patterned PTC and reduced aggressiveness. 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Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have not been reported. Here, we determine the major oncogenic events in PTC from non-exposed Belarusian children and assess their clinicopathological correlations. Among the 34 tumors, 23 (67.6%) harbored one of the mutually exclusive oncogenes: 5 (14.7%) BRAFV600E, 4 (11.8%) RET/PTC1, 6 (17.6%) RET/PTC3, 2 (5.9%) rare fusion genes, and 6 (17.6%) ETV6ex4/NTRK3. No mutations in codons 12, 13, and 61 of K-, N- and H-RAS, BRAFK601E, or ETV6ex5/NTRK3 or AKAP9/BRAF were detected. Fusion genes were significantly more frequent than BRAFV600E (p = 0.002). Clinicopathologically, RET/PTC3 was associated with solid growth pattern and higher tumor aggressiveness, BRAFV600E and RET/PTC1 with classic papillary morphology and mild clinical phenotype, and ETV6ex4/NTRK3 with follicular-patterned PTC and reduced aggressiveness. The spectrum of driver mutations in sporadic childhood PTC in Belarus largely parallels that in Chernobyl PTC, yet the frequencies of some oncogenes may likely differ from those in the early-onset Chernobyl PTC; clinicopathological features correlate with the oncogene type.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>34282777</pmid><doi>10.3390/cancers13133374</doi><orcidid>https://orcid.org/0000-0003-2844-3121</orcidid><orcidid>https://orcid.org/0000-0002-2744-8046</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Children Children & youth Chromosomes Codons Families & family life Genes Girls Growth patterns H-Ras protein Kinases Lymphatic system Metastasis Morphology Multivariate analysis Mutation Papillary thyroid carcinoma Phenotypes Radiation Ret protein Thyroid cancer Tumors Ultrasonic imaging |
| title | Major Oncogenic Drivers and Their Clinicopathological Correlations in Sporadic Childhood Papillary Thyroid Carcinoma in Belarus |
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