Gene panel (includes 26 genes)

Basic characteristics of the clinical phenotype
Malignant tumors originating from mesenchymal tissue (including connective tissue and muscle) are called "sarcomas". Sarcoma accounts for 12.6% of all malignant tumors in children and adolescents under the age of 19, but is rare in adults.

Sarcomas fall into two categories, soft tissue sarcomas, which account for the majority of sarcomas, and malignant primary bone tumors, which account for approximately 10%. The clinical manifestation of sarcoma includes local pain and swelling or local redness of the skin, heat, joint effusion, pain and limitation of the activity of the limbs or joints, etc. The etiology of sarcoma is unknown and the pathogenesis is unclear. Although relatively rare, sarcomas can occur anywhere in the body and arise in connective tissues such as bones, muscles, tendons, nerves, fat, cartilage, and blood vessels.

However, mutations in some genes have been reported to be associated with an increased risk of sarcoma. This test included genes associated with both soft tissue sarcoma and osteosarcoma.

Mutations in the TP53, RB1, NF1, SDHA, SDHB, SDHC, and SDHD genes are frequently found in sarcomas. The tumor suppressor gene TP53 is the most commonly mutated gene in human cancer, which also increases the risk of other cancers such as melanoma, breast cancer, and thyroid cancer. In sporadic cancers, the prevalence of TP53 variants in somatic cells is 10% to 60%. p53 is inactivated by the missense mutation, thereby abrogating a full array of antiproliferative and growth inhibitory responses.

Mutant p53 protein has carcinogenic effects and promotes tumor development. RB1, also a tumor suppressor gene, plays a major role in sarcoma formation. A significant enrichment of pathogenic variation in ATM and ATR genes, which are associated with DNA damage sensing, has been reported. Germline mutations in the mitochondrial complex II enzyme succinate dehydrogenase (SDH) are frequently found in gastrointestinal stromal tumors. In addition to these genes, unexpected pathogenic variants in ERCC2 that may affect DNA binding, DNA damage sensing, helicase activity and basal transcription were confirmed.

Indications  for Referral/ Clinical Significance:

Candidates for this test are all patients with a clinical (medical) or family history suggesting that the etiology of the disease is due to hereditary genetic changes. The test is offered to patients in whom the most common mutations are not detected using Sanger sequencing of the most commonly affected genes.

This test is specifically intended for the analysis of inherited germline mutations and is not suitable for the study of somatic mutations in tumor tissue.

Patients with a personal or family history suggestive of hereditary sarcoma syndrome. Important features suggestive of hereditary sarcoma may include onset of cancer before age 55, more than one primary cancer in one person, and multiple affected people in the family with a history of hematologic disease, disease of the pancreas, stomach, thyroid, brain, breast , kidney or colon cancer. After consideration of the patient's clinical and family history, this test may be appropriate for some pediatric patients. This test is designed to detect individuals with a pathogenic germline variant and has not been validated to detect mosaicism below the 20% level. It should not be tested on tumor tissue.

Method: Next-generation sequencing.

The method involves bidirectional DNA sequencing of all coding exons and intron-exon boundaries of target genes. The laboratory offers Sanger sequencing of a single exon or a pair of exons in the patient's relatives to determine carrier status in cases where the mutation is known (Test #182).

Sensitivity of the method: depends on G-C and A-T content, as well as the presence of segmentally duplicated genes.

What does the test involve?
· DNA isolation and sample storage.
· Parallel sequencing including bidirectional DNA sequencing of all coding exons and intron-exon boundaries of target genes
· Bioinformatic analysis of sequencing data. For each patient, only data for the gene(s) of interest were analyzed.
· Forming a written result of the genetic test.
· Diagnostic interpretation of results and genetic counseling.

Biological material: Venous blood or DNA
For more information, please read the "Biological material requirements and shipping information" carefully.