Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients
BackgroundGenome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the CHEK1 gene. Despite its well-established role in homologous recombination, germl...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1380093/full |
| _version_ | 1797208822047047680 |
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| author | Jun Qian Min Peng Yanan Li Wei Liu Xinwei Zou Huafei Chen Sujuan Zhou Sheng Xiao Jinhua Zhou |
| author_facet | Jun Qian Min Peng Yanan Li Wei Liu Xinwei Zou Huafei Chen Sujuan Zhou Sheng Xiao Jinhua Zhou |
| author_sort | Jun Qian |
| collection | DOAJ |
| description | BackgroundGenome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the CHEK1 gene. Despite its well-established role in homologous recombination, germline mutations in CHEK1 are rarely reported.Case presentationIn this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in KRAS, PPP2R1A, and PIK3R1. Importantly, her paired peripheral blood cells harbored a germline CHEK1 mutation, CHEK1 exon 6 c.613 + 2T>C, which was also found in her father. Unfortunately, the CHEK1 status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the CHEK1 gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation.ConclusionThis case highlights a rare germline CHEK1 mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types. |
| first_indexed | 2024-04-24T09:44:54Z |
| format | Article |
| id | doaj.art-e5e40f5c12b3413a932b3dbc5ff9b635 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-24T09:44:54Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e5e40f5c12b3413a932b3dbc5ff9b6352024-04-15T04:17:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-04-011410.3389/fonc.2024.13800931380093Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patientsJun Qian0Min Peng1Yanan Li2Wei Liu3Xinwei Zou4Huafei Chen5Sujuan Zhou6Sheng Xiao7Jinhua Zhou8Department of Gynecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaMolecular Genetics Laboratory, Suzhou Sano Precision Medicine Ltd., Suzhou, ChinaDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaMolecular Genetics Laboratory, Suzhou Sano Precision Medicine Ltd., Suzhou, ChinaMolecular Genetics Laboratory, Suzhou Sano Precision Medicine Ltd., Suzhou, ChinaDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaBackgroundGenome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the CHEK1 gene. Despite its well-established role in homologous recombination, germline mutations in CHEK1 are rarely reported.Case presentationIn this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in KRAS, PPP2R1A, and PIK3R1. Importantly, her paired peripheral blood cells harbored a germline CHEK1 mutation, CHEK1 exon 6 c.613 + 2T>C, which was also found in her father. Unfortunately, the CHEK1 status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the CHEK1 gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation.ConclusionThis case highlights a rare germline CHEK1 mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types.https://www.frontiersin.org/articles/10.3389/fonc.2024.1380093/fullCHEK1germline mutationsplicing errorovarian cancerinherited cancer |
| spellingShingle | Jun Qian Min Peng Yanan Li Wei Liu Xinwei Zou Huafei Chen Sujuan Zhou Sheng Xiao Jinhua Zhou Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients Frontiers in Oncology CHEK1 germline mutation splicing error ovarian cancer inherited cancer |
| title | Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients |
| title_full | Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients |
| title_fullStr | Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients |
| title_full_unstemmed | Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients |
| title_short | Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients |
| title_sort | case report a germline chek1 c 613 2t c leads to a splicing error in a family with multiple cancer patients |
| topic | CHEK1 germline mutation splicing error ovarian cancer inherited cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1380093/full |
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