Germline SMARCA4 mutations in patients with ovarian small cell carcinoma of hypercalcemic type
| Autor: | Dorota Nowakowska, Agnieszka Dansonka-Mieszkowska, Jolanta Kupryjanczyk, Agnieszka Budzilowska, Bozena Konopka, Lukasz Szafron, Joanna Moes-Sosnowska, Agnieszka Podgorska, Joanna Plisiecka-Halasa, Iwona K. Rzepecka |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Proband
Adult Male Immature teratoma Biology medicine.disease_cause Germline SMARCA4 mutation Young Adult Germline mutation Ovarian cancer Carcinoma medicine Humans Genetics(clinical) Pharmacology (medical) Carcinoma Small Cell Genetics (clinical) Germ-Line Mutation Medicine(all) Ovarian Neoplasms Mutation Research DNA Helicases Infant Nuclear Proteins General Medicine Middle Aged medicine.disease Penetrance Ovarian Small Cell Carcinoma Pedigree Small-cell carcinoma of hypercalcemic type Parotid gland carcinoma Child Preschool Immunology Cancer research Hypercalcemia Female Transcription Factors |
| Zdroj: | Orphanet Journal of Rare Diseases |
| ISSN: | 1750-1172 |
| Popis: | Background SMARCA4 mutations have recently been identified as driving lesions of the ovarian small cell carcinoma of hypercalcemic type (SCCHT). Familial occurrence of this neoplasm was described previously. Methods We looked for germline SMARCA4 alterations in eight patients with the SCCHT. DNA was extracted from probands’ and their relatives’ blood. The SMARCA4 coding sequence, previously found altered in all the tumors, was PCR amplified and sequenced in the germline DNA. Results Two patients carried a heterozygous germline SMARCA4 alteration: c.3760G > T and c.2352insG, respectively. The analysis of the probands’ next of kins revealed that the c.3760G > T mutation was inherited by the proband and her sister from their father, and the sisters’ four children also carried the mutation. The proband’s sister was diagnosed with a carcinoma of the parotid gland at age 2. A brother of the other proband was tested negative. Conclusions Our study suggests that some women develop the ovarian SCCHT due to the inherited or possibly de novo-occurring germline alterations in the SMARCA4 gene, however, its penetrance appears limited. Nevertheless, because of high aggressiveness of the SCCHT, a molecular diagnostics of the SMARCA4 gene and careful follow-up should be offered to patients with this cancer and their families. |
| Databáze: | OpenAIRE |
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