Abstract
BackgroundSMARCA4 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.MethodsWe 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.ResultsTwo 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.ConclusionsOur 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.
Highlights
SMARCA4 mutations have recently been identified as driving lesions of the ovarian small cell carcinoma of hypercalcemic type (SCCHT)
Moes-Sosnowska et al Orphanet Journal of Rare Diseases (2015) 10:32 other groups have found SMARCA4 mutations in this neoplasm [13,14,15] and all these findings suggest that the SCCHT is an ovarian rhabdoid tumor
In this study we present germline alterations of the SMARCA4 gene in two patients diagnosed with the SCCHT; one of these alterations was present in three generations of the proband’s relatives
Summary
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. A small cell carcinoma of the ovary of hypercalcemic type (SCCHT) is a rare and highly malignant neoplasm affecting young females. In the largest published group of patients the age of onset ranged from 9 to 43 years (median 24 years). The predominant population is that of small undifferentiated ovoid cells. There are foci of large cells with eosinophilic cytoplasm, with or without eccentrically displaced nuclei (rhabdoid features). The SCCHT grows rapidly and shows poor response to available chemotherapies.
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