title: Germline SMARCA4 mutations in patients with ovarian small cell carcinoma of hypercalcemic type.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. joamoes@gmail.com.
authors.forename: Joanna
authors.initials: J
authors.lastname: Moes-Sosnowska
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. lukszafron@gmail.com.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Szafron
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. donow@coi.waw.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. agad@coi.waw.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dansonka-Mieszkowska
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. agnieszka.budzilowska@coi.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Budzilowska
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. bkonopka@coi.waw.pl.
authors.forename: Bozena
authors.initials: B
authors.lastname: Konopka
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. jopliha@coi.waw.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Plisiecka-Halasa
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. ag.podgorski@yahoo.de.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Podgorska
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. ik.rzepecka@gmail.com.
authors.forename: Iwona K
authors.initials: IK
authors.lastname: Rzepecka
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. jkupry@coi.waw.pl.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kupryjanczyk
mesh_terms: D000328:Adult; D018288:Carcinoma, Small Cell / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D006934:Hypercalcemia; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000145:classification / Q000378:metabolism*; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases