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Personalised Medicine

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Personalised Medicine Focusing on Personalised Medicine VASCULAR MALFORMATIONS AND OVERGROWTH PANEL Vascular Malformations (VaMs) encompass a wide range of lesions and can involve arterial, capillary, venous or lymphatic endothelium.[1] VaMs can be attributed to the presence of a somatic mutations, or the presence of both a somatic and inherited germline mutation.[1] The mutations affect proliferation, migration, adhesion, differentiation, and survival of endothelial cells.1] The Vascular Malformations and Overgrowth Panel has been designed to target genes associated with a range of Vascular Malformations and Overgrowth Syndromes, including: • Capillary malformations, the most common type of vascular malformation, associated with GNAQ mutations.[2] • Lymphatic malformations, commonly associated with PIK3CA mutations.[1] • Sporadic venous malformations also associated with PIK3CA mutations. Mutations in MAP3K3 have also been identified in patients with Verrucous venous malformations.[1] • Vascular anomalies are major components of several types of overgrowth syndromes such as Proteus syndrome, caused by AKT1 mutations, and CLOVES syndrome, associated with PIK3CA mutations.[2] Mutations associated with VaMs often occur in genes that are part of the RAS/ MEK/ERK and/or AKT/PI3K/mTOR pathways. [1] Inhibitors targeting key players of these signaling pathways have been identified in recent studies, which may offer unprecedented therapeutic opportunities for Vascular anomalies and Overgrowth Syndromes. For example, Vascular anomalies with mutations affecting the AKT/PI3K/mTOR pathway have been shown to respond to mTOR inhibitors.[1] What Genes are Covered by the Vascular Sample Requirements Malformations and Overgrowth Panel? Testing can be performed on both somatic and germline samples. The Vascular Malformations and Overgrowth Panel covers 27 • Somatic sequencing – 10 -15 x unstained, uncoated FFPE genes associated with a range of Vascular Malformations and slides & 1 H&E from a recent biopsy Overgrowth syndromes: • Germline Sequencing – 1 x EDTA blood sample ACVRL1 KRIT1 AKT1 MAP2K1 Technical Information AKT3 MAP3K3 BRAF MTOR CCND2 NRAS This test is intended to be used and be interpreted in CDKN1C PIK3CA conjunction with all other available clinical and laboratory ELMO2 PIK3R1 information when evaluating treatment options. Testing targets ENG PIK3R2 the coding regions of the listed genes, including targeted EPHB4 PTEN coding regions and intron-exon boundaries, but does not detect GLMN RASA1 GNA11 SMAD4 mutations that are outside of the targeted area and does not GNAQ STAMBP detect copy number variations, deep intronic variants, large HRAS TEK exonic deletions, translocations or methylation status. Testing KRAS does not cover the entire gene sequence. How Do I Organise Testing? Download Request Genomics For Life Return your sample Genomics For Results sent to Form, complete and arranges samples to Genomics For Life Life completes nominated health return to for testing for testing requested testing care professional Genomics For Life Toll Free: 1800 445 433 Fax: 1300 658 893 Email: [email protected] Web: www.genomicsforlife.com.au References 1. Zúñiga-Castillo, M., Teng, C., & Teng, J. (2019). Genetics of vascular malformation and therapeutic implications. Current Opinion In Pediatrics, 31(4), 498-508. doi: 10.1097/mop.0000000000000794 2. Greene, A., & Goss, J. (2018). Vascular Anomalies. Plastic And Reconstructive Surgery, 141(5), 709e-717e. doi: 10.1097/prs.0000000000004294.
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