Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome
Abstract Background Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), caused by heterozygous germline pathogenic variants in the FH, confers an increased risk for cutaneous and uterine leiomyomas and renal cancer. Methods About 13,722 advanced cancer patients, including 560 with rena...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-08-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1293 |
| _version_ | 1797301081274843136 |
|---|---|
| author | Kelsey E. Breen Maria I. Carlo Yelena Kemel Anna Maio Ying‐Bei Chen Liying Zhang Ozge Ceyhan‐Birsoy Diana Mandelker |
| author_facet | Kelsey E. Breen Maria I. Carlo Yelena Kemel Anna Maio Ying‐Bei Chen Liying Zhang Ozge Ceyhan‐Birsoy Diana Mandelker |
| author_sort | Kelsey E. Breen |
| collection | DOAJ |
| description | Abstract Background Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), caused by heterozygous germline pathogenic variants in the FH, confers an increased risk for cutaneous and uterine leiomyomas and renal cancer. Methods About 13,722 advanced cancer patients, including 560 with renal cell carcinoma, had germline analysis performed in the context of tumor‐normal sequencing under an IRB approved protocol. Results We report two unrelated individuals with early onset kidney cancer who both carried the c.914C > T (p.Phe305Ser) germline variant in the FH. Both tumors exhibited loss of FH staining by immunohistochemistry and/or positive 2SC staining. Subsequent familial testing discovered that a daughter of a proband who carried the variant had both cutaneous and uterine leiomyomas. Conclusion This combination of evidence suggests that the FH c.914C > T (p.Phe305Ser) is pathogenic for HLRCC. |
| first_indexed | 2024-03-07T23:16:17Z |
| format | Article |
| id | doaj.art-bdda7838b988417e86662bd355f7300b |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:16:17Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-bdda7838b988417e86662bd355f7300b2024-02-21T11:08:50ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-08-0188n/an/a10.1002/mgg3.1293Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndromeKelsey E. Breen0Maria I. Carlo1Yelena Kemel2Anna Maio3Ying‐Bei Chen4Liying Zhang5Ozge Ceyhan‐Birsoy6Diana Mandelker7Department of Medicine Memorial Sloan Kettering Cancer Center New York City NY USADepartment of Medicine Memorial Sloan Kettering Cancer Center New York City NY USANiehaus Center for Inherited Cancer Genomics Sloan Kettering InstituteMemorial Sloan Kettering Cancer Center New York City NY USADepartment of Medicine Memorial Sloan Kettering Cancer Center New York City NY USADepartment of Pathology Memorial Sloan Kettering Cancer Center New York City NY USADepartment of Pathology and Laboratory Medicine University of California Los Angeles CA USADepartment of Pathology Memorial Sloan Kettering Cancer Center New York City NY USADepartment of Pathology Memorial Sloan Kettering Cancer Center New York City NY USAAbstract Background Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), caused by heterozygous germline pathogenic variants in the FH, confers an increased risk for cutaneous and uterine leiomyomas and renal cancer. Methods About 13,722 advanced cancer patients, including 560 with renal cell carcinoma, had germline analysis performed in the context of tumor‐normal sequencing under an IRB approved protocol. Results We report two unrelated individuals with early onset kidney cancer who both carried the c.914C > T (p.Phe305Ser) germline variant in the FH. Both tumors exhibited loss of FH staining by immunohistochemistry and/or positive 2SC staining. Subsequent familial testing discovered that a daughter of a proband who carried the variant had both cutaneous and uterine leiomyomas. Conclusion This combination of evidence suggests that the FH c.914C > T (p.Phe305Ser) is pathogenic for HLRCC.https://doi.org/10.1002/mgg3.1293carcinomafumarate hydrataseleiomyomatosismutationrenal cell |
| spellingShingle | Kelsey E. Breen Maria I. Carlo Yelena Kemel Anna Maio Ying‐Bei Chen Liying Zhang Ozge Ceyhan‐Birsoy Diana Mandelker Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome Molecular Genetics & Genomic Medicine carcinoma fumarate hydratase leiomyomatosis mutation renal cell |
| title | Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome |
| title_full | Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome |
| title_fullStr | Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome |
| title_full_unstemmed | Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome |
| title_short | Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome |
| title_sort | fumarate hydratase c 914t c p phe305ser is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome |
| topic | carcinoma fumarate hydratase leiomyomatosis mutation renal cell |
| url | https://doi.org/10.1002/mgg3.1293 |
| work_keys_str_mv | AT kelseyebreen fumaratehydratasec914tcpphe305serisapathogenicvariantassociatedwithhereditaryleiomyomatosisandrenalcellcancersyndrome AT mariaicarlo fumaratehydratasec914tcpphe305serisapathogenicvariantassociatedwithhereditaryleiomyomatosisandrenalcellcancersyndrome AT yelenakemel fumaratehydratasec914tcpphe305serisapathogenicvariantassociatedwithhereditaryleiomyomatosisandrenalcellcancersyndrome AT annamaio fumaratehydratasec914tcpphe305serisapathogenicvariantassociatedwithhereditaryleiomyomatosisandrenalcellcancersyndrome AT yingbeichen fumaratehydratasec914tcpphe305serisapathogenicvariantassociatedwithhereditaryleiomyomatosisandrenalcellcancersyndrome AT liyingzhang fumaratehydratasec914tcpphe305serisapathogenicvariantassociatedwithhereditaryleiomyomatosisandrenalcellcancersyndrome AT ozgeceyhanbirsoy fumaratehydratasec914tcpphe305serisapathogenicvariantassociatedwithhereditaryleiomyomatosisandrenalcellcancersyndrome AT dianamandelker fumaratehydratasec914tcpphe305serisapathogenicvariantassociatedwithhereditaryleiomyomatosisandrenalcellcancersyndrome |