Solid tumor panel – somatic mutation testing
Solid tumors are diseases characterized by the formation of an abnormal mass of tissue. They can be benign or malignant. Many solid tumors contain high numbers of somatic mutations, genetic changes that are not inherited but rather created within the tumor itself.
Find your genetic test
Mapping the individual genetic landscape of solid tumors
Somatic mutations in many different genes have been found in breast cancer cells. Variants in BRCA1 and BRCA2 genes which are known to be responsible for the inherited breast and ovarian cancer syndrome are also found in sporadic cancer. As carriers for these variants profit from a targeted therapy somatic analysis of these genes is also recommended in cases where there is no family history for inherited breast cancer syndrome. Other genes found with sequence variations and evidence for an impact on prognosis or treatment are AKT1, PIK3CA, PTEN, CDK4, CDK6, CDK6, RB1 and TP53.
Colorectal cancer (CRC) is a heterogeneous disease that is common in both men and women. In addition to lifestyle and environmental risk factors, gene defects can contribute to an inherited predisposition to CRC. A comprehensive study that sequenced more than 13,000 genes in a series of CRCs found that tumors accumulate an average of approximately 90 mutant genes with two-thirds relevant to CRC. In addition, each tumor studied had a distinct mutational gene signature. Somatic mutations in the genes BRAF, NRAS, KRAS, AKT1, PTEN, PIK3CA and SMAD4 have been found with altered progression and prognosis.
Melanoma is considered to be one of the most aggressive and treatment-resistant of all human cancers. It starts in melanocytes, which are cells found in the outermost layer of skin. Melanocytes make a brown pigment called melanin. Melanin protects the deeper layers of skin (the dermis and subcutis layers) from the harmful effects of the sun. Melaomas are found with an increasing incidence. In addition to the inherited melanoma syndrome gene, mutations in BRAF, CTNNB1, GNA11, GNAQ, KIT, MEK1 (MAP2K1) and NRAS can be found in approximately 70% of all melanomas including sporadic cases. In addition, mutations have also been described in melanoma. Genes with somatic mutations that participate in melanoma pathology are most commonly BRCA2, CDKN2A, CDK4 and TP53.
The genetic basis for neuroblastoma is not yet well understood. As sequence variation, ALK mutations have been identified. ALK mutations have been detected in 6–9% of tumor samples (Chen et al. 2008; George et al. 2008; Janoueix-Lerosey et al. 2008). There has also been some work published on the roles of ATRX mutations (Cheung et al. 2012). ATRX mutations are associated with patient age: younger patients’ tumors are less likely to harbor ATRX mutations (Cheung et al. 2012). Development of targeted therapeutics has focused on ALK.
Environmental exposures, smoking and genetic susceptibility are contributing factors to the lung cancer risk. Adenocarcinomas in patients who have never smoked frequently contain mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene, and those patients often respond to tyrosine kinase inhibitor drugs such as gefitinib and erlotinib, but usually develop drug resistance. Conversely, KRAS mutations are more common in individuals with a history of cigarette use and are associated with resistance to EGFR-tyrosine-kinase inhibitors.
Gastric cancer is the fourth most common cancer worldwide and the second leading cause of global cancer deaths. The identification of germline E-cadherin (CDH1) mutations in families with hereditary diffuse gastric cancer provided an early insight into the initial changes that promote gastric tumorogenesis and established the CDH1 gene as a tumor suppressor. Frequently mutated genes in the gastric cancer also include TP53, PIK3CA and ARID1A. In addition, the prevalence genetic screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers and FAT4 genomic deletions in 4% of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occur in 47% of the gastric cancers.
When to suggest the solid tumor panel
The solid tumor panel can be recommended for the following patients:
- Individuals with solid tumors where a mutational profile from multiple genes will affect diagnosis disease stratification, prognosis or treatment options.
Scientific articles on somatic mutations
Thrombocytopenia is a disorder of haematopoetic cells with predominant defects of platelets and it is defined as having a platelet count of less than 150,000 in mL of circulating blood, while the normal number of platelets ranges between 150,000 and 450,000 cells per mL of blood. Platelets are haemopoetic cells that play a primary role in haemostasis, interacting with subendothelium-bound von Willebrand factor (VWF) via the membrane glycoprotein complexes.
Robustness of comprehensive DNA- and RNA-based assays at diagnosis of acute myeloid leukemia using blood and bone marrow stored on filter cards
"Molecular analyses in hematologic malignancies gained considerable importance in the last decade at diagnosis and for minimal residual disease (MRD). In our study, we performed a comparison of state-of-the-art cytogenetics, FISH and molecular diagnostic assays based on standard liquid peripheral blood or bone marrow samples and on diagnostic material stored on filter cards."
The goals of somatic testing of solid tumors are to identify:
- The individual genetic landscape of the tumor by assessing multiple gene targets simultaneously
- Actionable variants within the genes known to be associated with response or resistance to specific cancer therapies
- Variants that may help to determine the prognosis for patients with solid tumors
- So far unknown variants in well described tumor genes which might be used for targeted therapies
- To finally establish a diagnosis that will reassure both patient and physician about the occurring health problem, in order to inform and to tailor the best therapeutic strategy for the patient
Benefits of solid tumorigenic testing:
- Covers 63 of the most important genes and associated mutations with 96% coverage of the coding regions
- Detects most actionable mutations with clear clinical relevance; EGFR/MAPK and PI3K pathways
- Enables rapid eligibility identification and patient stratification for clinical trials
- Allows longitudinal and serial molecular monitoring throughout the clinical trial process
- Does not require special shipping or storage provisions
- Employs expert analysis from a CLIA-certified lab
CENTOGENE´s solid tumor panel offers:
- Solid tumor panel includes the following genes: ABL1, AKT1, ALK, APC, AR, ARID1A, ASXL1, ATM, AXL, BRAF, CDH1, CDK4, CDKN2A, CTNNB1, DDR2, EGFR, ERBB2, FGFR1, FGFR2, FGFR3, FGFR4, GNA11, GNAQ, GNAS, HRAS, IDH1, IDH2, JAK2, JAK3, KDM6A, KDR, KIT, KRAS, MAP2K1, MET, MLH1, MLL, MLL2, MLL3, MTOR, NF1, NOTCH1, NRAS, NTRK3, PDGFRA, PDGFRB, PIK3CA, PIK3R1, PTCH1, PTEN, PTPN11, RB1, RET, ROS1, SMAD4, SMARCA4, SMARCB1, SMO, STK11, TP53, TSHR, TSC1, VHL
- The panel covers 96% of coding regions of all 63 tumor suppressor genes and oncogenes
- Mean coverage depth of >1,000x
- The turnaround time for the panel is ten working days
- Ten sections of 5–10µm thickness from the FFP tissue with areas of enriched tumor clearly marked accompanied with pathology report and oncology report in case of a relapse testing
- 1 µg of DNA from tumor-enriched section
- 1 ml of EDTA blood or 1 µg DNA from normal tissue (for example: buccal swab) as a recommended control
- Solid tumor panel utilizes NGS sequencing on Ion Proton Platform