SMARCA4 germline gene mutation in a patient with epithelial ovarian: A case report

Abstract

BackgroundSMARCA4 is gene whose protein product participates in chromatin remodeling. Somatic mutations in this gene are associated with non-small cell lung cancer and malignant rhabdoid tumors, and both germline and somatic mutations are seen with small cell carcinoma of the ovary, hypercalcemic type. To date, there are no data identifying an association with more common epithelial carcinomas of the ovary.CaseThe patient is a 57-year-old female without any significant family history of cancer, diagnosed with high-grade serous carcinoma of the ovary. Per guideline, she underwent genetic testing, and was found to have a deleterious germline SMARCA4 mutation. She was treated with standard chemotherapy and an optimal tumor reduction, with a complete response to treatment.ConclusionThe etiology of this patient's high-grade serous carcinoma is unknown. If the SMARCA4 gene plays a role in serous ovarian carcinoma it is with variable expressivity. Further investigation into the role of SMARCA4 as a susceptibility gene for epithelial ovarian cancer is warranted.

An In-Depth Look at Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Clinical Implications from Recent Molecular Findings

“…In contrast, SCCOHT is predominantly associated with SMARCA4 (BRG1) mutations and rarely with SMARCB1 (INI1) 68, 95. SMARCA4 (BRG1) mutations can be regarded as the hallmark of SCCOHT although deleterious germline SMARCA4 mutation has been reported in one high grade serous carcinoma to date 96. A recent molecular study demonstrated that the genomic and epigenomic signature of SCCOHT are similar to those of AT/RT 97.…”

“…Thereafter, Foulkes WD, et al 62 have suggested that SCCOHT should be renamed as malignant rhabdoid tumors of the ovary having SMARCA4 mutations. This conception is further supported by SMARCA4-deficient undifferentiated uterine sarcoma (malignant rhabdoid tumor of the uterus), which showed rhabdoid morphology, SMARCA4 loss by immunohistochemistry and recurrent SMARCA4 mutations and few other molecular alterations 96. However, Soslow RA and colleagues 36 think that the nomenclature change is premature currently due to the extensive accumulation of literatures under the traditional term SCCOHT.…”

Diagnosis of a SMARCA4‐deficient undifferentiated tumor using multigene panel testing: A case report

“…From the investigation of unclassified malignancies, somatic variation in SWI/SNF‐related, matrix‐associated, actin‐dependent regulator of chromatin, subfamily A, member 4 ( SMARCA4 ) is recognized as one of the driver mutations in undifferentiated tumors 6 . It is found on chromosome 19p13.2 and is part of the SWI/SNF chromatin‐remodeling complex consisting of 40 exons 7 . SMARCA4 encodes Brm/Swi2‐related gene 1 ( BRG1 ), a tumor suppressor and catalytic subunit of the SWI/SNF chromatin‐remodeling complex.…”

“… 6 It is found on chromosome 19p13.2 and is part of the SWI/SNF chromatin‐remodeling complex consisting of 40 exons. 7 SMARCA4 encodes Brm/Swi2‐related gene 1 ( BRG1 ), a tumor suppressor and catalytic subunit of the SWI/SNF chromatin‐remodeling complex. SWI/SNF complexes regulate many tumor‐suppressive processes, including DNA repair.…”

Epigenetic Crosstalk between the Tumor Microenvironment and Ovarian Cancer Cells: A Therapeutic Road Less Traveled

“…Most interestingly, tumors with ARID1A mutations acquire sensitivity to pan-HDAC inhibitors, thus making ARID1A-bearing cancers attractive for HDAC-based therapy [ 70 ]. SMARCA4 is frequently (over 90%) mutated in ovarian small cell carcinomas of the hypercalcemic type [ 71 , 72 ], however, to our knowledge, the first case of a germline SMARCA4 mutation in a patient with HGSOC was recently reported [ 73 ]. Further investigation on the role and clinical applicability of SMARCA4 and ARID1A in HGSOC is warranted [ 74 , 75 ].…”