Incidence of the <i>CHEK2</i> Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma
The <i>CHEK2</i> gene is involved in the repair of damaged DNA. <i>CHEK2</i> germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether <i>C...
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| Language: | English |
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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/2072-6694/13/3/470 |
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| author | Danuta Gąsior-Perczak Artur Kowalik Krzysztof Gruszczyński Agnieszka Walczyk Monika Siołek Iwona Pałyga Sławomir Trepka Estera Mikina Tomasz Trybek Janusz Kopczyński Agnieszka Suligowska Rafał Ślusarczyk Agnieszka Gonet Jarosław Jaskulski Paweł Orłowski Magdalena Chrapek Stanisław Góźdź Aldona Kowalska |
| author_facet | Danuta Gąsior-Perczak Artur Kowalik Krzysztof Gruszczyński Agnieszka Walczyk Monika Siołek Iwona Pałyga Sławomir Trepka Estera Mikina Tomasz Trybek Janusz Kopczyński Agnieszka Suligowska Rafał Ślusarczyk Agnieszka Gonet Jarosław Jaskulski Paweł Orłowski Magdalena Chrapek Stanisław Góźdź Aldona Kowalska |
| author_sort | Danuta Gąsior-Perczak |
| collection | DOAJ |
| description | The <i>CHEK2</i> gene is involved in the repair of damaged DNA. <i>CHEK2</i> germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether <i>CHEK2</i> germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. <i>CHEK2</i> mutations were found in 240 (15.5%) of patients. A <i>CHEK2</i> I157T missense mutation was found in 12.3%, and <i>CHEK2</i> truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (<i>p</i> = 0.038), and were associated with vascular invasion (OR, 6.91; <i>p</i> < 0.0001) and intermediate or high initial risk (OR, 1.92; <i>p</i> = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the <i>CHEK2</i> truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease. |
| first_indexed | 2024-03-09T03:39:44Z |
| format | Article |
| id | doaj.art-b554e4b9f1304ec19d70db01c917f6fb |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T03:39:44Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b554e4b9f1304ec19d70db01c917f6fb2023-12-03T14:43:51ZengMDPI AGCancers2072-66942021-01-0113347010.3390/cancers13030470Incidence of the <i>CHEK2</i> Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid CarcinomaDanuta Gąsior-Perczak0Artur Kowalik1Krzysztof Gruszczyński2Agnieszka Walczyk3Monika Siołek4Iwona Pałyga5Sławomir Trepka6Estera Mikina7Tomasz Trybek8Janusz Kopczyński9Agnieszka Suligowska10Rafał Ślusarczyk11Agnieszka Gonet12Jarosław Jaskulski13Paweł Orłowski14Magdalena Chrapek15Stanisław Góźdź16Aldona Kowalska17Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandDepartment of Molecular Diagnostics, Holycross Cancer Center, Artwińskiego 3, 25-734 Kielce, PolandDepartment of Molecular Diagnostics, Holycross Cancer Center, Artwińskiego 3, 25-734 Kielce, PolandCollegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandGenetic Clinic, Holycross Cancer Center, 25-734 Kielce, PolandCollegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandCollegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandEndocrinology Clinic, Holycross Cancer Center, Artwińskiego 3, 25-734 Kielce, PolandEndocrinology Clinic, Holycross Cancer Center, Artwińskiego 3, 25-734 Kielce, PolandSurgical Pathology, Holycross Cancer Center, Artwińskiego 3, 25-734 Kielce, PolandEndocrinology Clinic, Holycross Cancer Center, Artwińskiego 3, 25-734 Kielce, PolandCollegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandCollegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandCollegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandCollegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandFaculty of Natural Sciences, Jan Kochanowski University, 25-406 Kielce, PolandCollegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandCollegium Medicum, Jan Kochanowski University, 25-317 Kielce, PolandThe <i>CHEK2</i> gene is involved in the repair of damaged DNA. <i>CHEK2</i> germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether <i>CHEK2</i> germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. <i>CHEK2</i> mutations were found in 240 (15.5%) of patients. A <i>CHEK2</i> I157T missense mutation was found in 12.3%, and <i>CHEK2</i> truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (<i>p</i> = 0.038), and were associated with vascular invasion (OR, 6.91; <i>p</i> < 0.0001) and intermediate or high initial risk (OR, 1.92; <i>p</i> = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the <i>CHEK2</i> truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease.https://www.mdpi.com/2072-6694/13/3/470papillary thyroid cancer<i>CHEK2</i><i>CHEK2</i> missense mutation<i>CHEK2</i> truncating mutationrisk stratificationIVS2 + 1G > |
| spellingShingle | Danuta Gąsior-Perczak Artur Kowalik Krzysztof Gruszczyński Agnieszka Walczyk Monika Siołek Iwona Pałyga Sławomir Trepka Estera Mikina Tomasz Trybek Janusz Kopczyński Agnieszka Suligowska Rafał Ślusarczyk Agnieszka Gonet Jarosław Jaskulski Paweł Orłowski Magdalena Chrapek Stanisław Góźdź Aldona Kowalska Incidence of the <i>CHEK2</i> Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma Cancers papillary thyroid cancer <i>CHEK2</i> <i>CHEK2</i> missense mutation <i>CHEK2</i> truncating mutation risk stratification IVS2 + 1G > |
| title | Incidence of the <i>CHEK2</i> Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma |
| title_full | Incidence of the <i>CHEK2</i> Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma |
| title_fullStr | Incidence of the <i>CHEK2</i> Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma |
| title_full_unstemmed | Incidence of the <i>CHEK2</i> Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma |
| title_short | Incidence of the <i>CHEK2</i> Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma |
| title_sort | incidence of the i chek2 i germline mutation and its impact on clinicopathological features treatment responses and disease course in patients with papillary thyroid carcinoma |
| topic | papillary thyroid cancer <i>CHEK2</i> <i>CHEK2</i> missense mutation <i>CHEK2</i> truncating mutation risk stratification IVS2 + 1G > |
| url | https://www.mdpi.com/2072-6694/13/3/470 |
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