Highlights
- •SCCOHT and SMARCA4-DUS are morphological and genetically related tumors driven by loss of function mutations in SMARCA4.
- •These tumors affect young women and generally carry a poor prognosis.
- •Identification of germline mutations in SMARCA4 is critical to providing counseling and treatment to affected individuals.
Abstract
Objective
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and SMARCA4-deficient
undifferentiated uterine sarcoma (SMARCA4-DUS) are rare and aggressive tumors, primarily
affecting pre- and perimenopausal women. Inactivating SMARCA4 mutations are thought to be the driving molecular events in the majority of these
tumors. Here, we report the clinical course of a family with germline SMARCA4 mutation and compare large cohorts of these rare tumor types.
Methods
We extracted clinico-pathological medical record data for the family with germline
SMARCA4 mutation. Clinico-genomic data from SCCOHT and SMARCA4-DUS cohorts were retrospectively
extracted from the archives of a large CLIA-certified reference molecular laboratory.
Results
We identified a single family with an inherited germline SMARCA4 mutation, in which two different family members developed either SCCOHT or SMARCA4-DUS,
both of whom died within one year of diagnosis, despite aggressive surgical, chemotherapy
and immunotherapy treatment. Retrospective comparative analysis of large SCCOHT (n = 48)
and SMARCA4-DUS (n = 17) cohorts revealed that SCCOHT patients were younger (median
age: 28.5 vs. 49.0) and more likely to have germline SMARCA4 alterations (37.5% vs. 11.8%) than SMARCA4-DUS patients.
Conclusions
Growing understanding of the role SMARCA4 plays in the pathogenesis of these rare cancers may inform recommended genetic testing
and counseling in families with these tumor types.
Keywords
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Article info
Publication history
Published online: January 15, 2020
Accepted:
October 28,
2019
Received in revised form:
October 23,
2019
Received:
August 17,
2019
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
