This test analyzes the SMARCA4 gene. Pathogenic variants in SMARCA4 are associated with small cell carcinoma of the ovary hypercalcemic type (SCCOHT) and rhabdoid tumor predisposition syndrome type 2 (RTPS).
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
SMARCA4 can also be ordered as part of a broader panel to test for different types of hereditary cancer conditions. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.
Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a specific type of ovarian cancer that can be distinguished from others by the presence of hypercalcemia (seen in one-third of cases), early age of onset (average 25 years), and small, hyperchromatic cells with brisk mitotic activity. SCCOHT can be difficult to differentiate from other ovarian cancers because there is significant pathology overlap with sex cord-stromal tumors, germ cell tumors, endometrial stromal sarcoma, and neuroblastoma—among others. It has been suggested that SCCOHT is a rhabdoid tumor and should be referred to as malignant rhabdoid tumor of the ovary (MRTO).
Individuals with a pathogenic variant in SMARCA4 have an increased risk of malignancy compared to the average person, but not everyone with a pathogenic variant will actually develop cancer. Further, the same variant can present differently, even among family members. The lifetime risks for SCCOHT in individuals with a pathogenic SMARCA4 variant is currently unclear.
SCCOHT can occur in isolation, but approximately 50% of cases are due to heritable pathogenic variants in the SMARCA4 gene.
SCCOHT is inherited in an autosomal dominant pattern, but it is uncommon for the condition to actually be inherited from a parent. Most cases of SCCOHT occur as the result of a spontaneous de novo mutation.
SCCOHT accounts for less than 1% of all ovarian cancer. Approximately 50% of SCCOHT cases are due to pathogenic variants in the SMARCA4 gene.
Genetic testing of the SMARCA4 gene is reasonable to consider for any individual with a personal and/or family history of any of the following:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|