Genomic Medicine

Genomic Medicine

SR NOTESTTEST COMPONENTSMETHODSPECIMEN/TRANSPORTTATCLINICAL APPLICATIONS
1OncomineA panel of 52 genes.NGSTumor FFPE, Room Tempt.15To determine targeted therapies, prognosis and management of patient. Analyzes hotspots, SNVs, indels, CNVs, and gene fusions.
2Lung cancer panel.A panel of 22 genes.NGSTumor FFPE/Pleural fluid, Room Tempt.10Mutation testing to aid in selection of tyrosine kinase inhibitor (TKI). EGFR pathogenic mutation predicts reponse to TKI while T790M mutation predicts resistance to first generation TKI and response to Osimertinib. KRAS pathogenic mutations are negative predictor of response TKIs erlotinib and gefitinib. Several point mutations in the ALK kinase domain result in aquired resistance to the ALK TKI, crizotinib. PIK3CA mutations E542, E545 and H1047 may result in aquired resistance to EGFR TKI therapy.
3Colon cancer panel.A panel of 22 genes.NGSTumor FFPE, Room Tempt.10To identify targeted therapies against lung tumor of patients. To identify resistance against Cetuximab, Panitumumab, Prognosis.
4Comprehensive cancer panel.A panel of 400 genes.NGSTumor FFPE, Room Tempt.20To assess prognosis and guiding treatment of individuals with solid tumors. These data can also be used to help determine clinical trial eligibility for patients with mutations in genes not amenable to current FDA-approved targeted therapies.
5Cancer Seek- L Liquid BiopsyA panel of 22 genes.Liquid biopsy, NGSWhole blood 10ml in Streck tube (Cell-Free DNA BCT Tube). Ambient: 5 days; Refrigerated: Unacceptable; Frozen: Unacceptable.15To identify targeted therapies against lung tumor of patients and determine mechanisms of resistance. EGFR pathogenic mutation predicts reponse to TKI while T790M mutation predicts resistance to first generation TKI and response to Osimertinib. KRAS pathogenic mutations are negative predictor of response TKIs erlotinib and gefitinib. Several point mutations in the ALK kinase domain result in aquired resistance to the ALK TKI, crizotinib. PIK3CA mutations E542, E545 and H1047 may result in aquired resistance to EGFR TKI therapy.
6Clinical exome sequencing.A panel of genes.NGSPreferred sample EDTA Blood (3ml x 3) Amniotic Fluid/ CVS will be accepted based on clinical criteria on special consideration. Specimen at room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.20Clinical exome sequencing (CES) is rapidly becoming a common molecular
diagnostic test for establishing a definitive molecular diagnosis of individuals with rare genetic disorders which can allow for:
-Better understanding of the natural history/prognosis
-Targeted management (anticipatory guidance, management changes, specific therapies)
-Predictive testing of at-risk family members
-Testing and exclusion of disease in siblings or other relatives
-Recurrence risk assessment
-Reproductive decision-making
Serving as a second-tier test for patients in whom previous genetic testing for specific syndromes was negative
Providing a potentially cost-effective alternative to establishing a molecular diagnosis compared to multiple independent molecular assays
7Familial/ Hereditary Cancer Panel (94 genes)A panel of GenesNGSEDTA Blood (3ml whole blood):Refrigerated Amniotic Fluid (15 ml): Room temperature. Unacceptable Conditions
Frozen specimens, Bloody specimens. CVS: Room temperature, Unacceptable Conditions Frozen specimens,Specimens preserved in formalin. 2-8 C tempt. for transport.
20Germline genetic testing can identify an individual’s hereditary risk for a number of cancers, including cancers of the breast, ovary, uterus, colon, stomach, thyroid and other primary sites. The identification of an inherited predisposition can have implications for clinical care, surveillance, chemoprevention, and preventive surgery. Screening should include, at minimum, a personal cancer history and a first- and second-degree relative cancer history that includes a description of the type of primary cancer, the age of onset, and the lineage (paternal versus maternal) of the family member.
8Neurofibromataosis Panel.coding region and intron-exon boundaries of the NF1 and NF2gene associated with NeurofibromatosisNGSPreferred sample EDTA Blood (3ml x 3) Amniotic Fluid/ CVS will be accepted based on clinical criteria on special consideration.20This test is used to screen for mutations in the genes responsible for NFP. This test helps in determining the necessity for screening in other family members. In cases of a positive finding in a patient of child bearing age, Preimplantation genetic diagnosis can be performed in most cases to help conceive a child without the pathogenic mutation.
9Tuberous Sclerosis.Coding region and certain intronic padding region of the TSC1 and TSC2 genes associated with Tuberous Sclerosis.NGSpreferred sample EDTA Blood (3ml x 3) Amniotic Fluid/ CVS will be accepted based on clinical criteria on special consideration. Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.20This test is used to screen for mutations in the genes responsible for TSC. This test helps in determining the necessity for screening in other family members. In cases of a positive finding in a patient of child bearing age, Preimplantation genetic diagnosis can be performed in most cases to help conceive a child without the pathogenic mutation.
10Breast cancer panel.Panel of BRCA1&2 GenesNGSEDTA Blood (3ml whole blood): Refrigerated. Temperature: Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable.20To confirm hereditary breast and ovarian cancer (HBOC) syndrome (BRCA1 and BRCA2 genes only).
11Gastro-intestinal Stromal Tumours (GISTs) Panel.CKIT (EXONS 9,11,13,14,17) and PDGFRA (EXONS 12,14,18)NGSTissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.10Detected − KIT mutation detected in exons 9, 11, 13 , 14, 17, 18, Exon 9 Requires an escalated dose of TKI for response Better response to sunitinib than imatinib
Exon 11 Associated with TKI sensitivity Exon 13 Primary (nontherapy associated) – associated with TKI sensitivity Secondary (acquired during therapy) – associated with
TKI resistance Exon 14 Secondary (acquired during therapy) – associated with TKI resistance Exon 17 D816V – associated with TKI resistance Primary – associated with TKI sensitivity
Secondary – associated with TKI resistance oExon 18 (rare) Secondary (acquired during therapy) – associated with TKI resistance. Detected – PDGFRA mutation detected in exons 12, 14, 18
Exon 12 – associated with tyrosine kinase inhibitor (TKI) sensitivity. Exon 14 – associated with tyrosine kinase inhibitor (TKI) sensitivity. Exon 18 (D842V and D846V) – associated with tyrosine kinase inhibitor (TKI) resistance.
12Glioma Panel.Detection of IDH1 and IDH2, CpG methylation within the MGMT gene promoterSanger sequencing.Tissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.10(1) Prognostication of newly diagnosed glioblastomas. (2) IDH1 and IDH2 mutations are associated with favorable outcome in all WHO grade gliomas. (3) SNP rs11554137 is associated with unfavorable prognosis. In AML patients IDh mutations indicate unfavorable prognosis if IDH1/IDH2 mutations appear with NPM1 mutations and in the absence of FLT3-ITD mutations. (4) Prognostication of newly diagnosed glioblastomas (5) Identifying newly diagnosed glioblastomas that may respond to alkylating chemotherapy (temozolomide) (6) Guiding therapy decision making for newly diagnosed glioblastomas in elderly patients (>60 years).
13Li Fraumeni syndrome.TP53 geneNGSEDTA Blood (3ml x 3). Temperature: Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable21To confirm clinical diagnosis of classic Li-Fraumeni syndrome
(LFS) or Li-Fraumeni-like syndrome (LFL).
14Multiple Endocrine Neoplasia type 1.MEN1 geneNGSEDTA Blood: Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable.20To confirm clinical diagnosis of MEN1
15Multiple Endocrine Neoplasia type 2MEN2 geneNGSEDTA Blood: Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable.20To confirm clinical diagnosis of MEN2
16EGFR (Epidermal Growth Factor Receptor)EGFRNGSAmbient: Indefinitely; Refrigerated: Indefinitely; Frozen: Unacceptable10 daysIdentifying non-small cell lung cancers that may respond to epidermal growth factor receptor-tyrosine kinase inhibitor therapies.
17ALK (Anaplastic Lymphoma Kinase)ALK rearrangement.NGSAmbient: Indefinitely; Refrigerated: Indefinitely; Frozen: Unacceptable10Identifying non-small cell lung cancers that may benefit from treatment with epidermal growth factor receptor-tyrosine kinase or anaplastic lymphoma kinase inhibitors
18KRAS (Kirsten Rat Sarcoma Virus) .KRASNGSAmbient: Indefinitely; Refrigerated: Indefinitely; Frozen: Unacceptable20 daysPathogenic mutation indicate response to tyrosine kinase inhibitor (TKI) therapy Erlotinib, Afatinib, Gefitinib. EGFR T790M predicts resistance to Erlotinib, Afatinib, Gefitinib while sensitivity to Osimertinib.
19NRAS (Neuroblastoma Ras Viral Oncogene)NRASNGSAmbient: Indefinitely; Refrigerated: Indefinitely; Frozen: Unacceptable20 daysPathogenic NRAS mutation is predictive of relative resistance to anti-EGFR therapy in
colorectal cancer.
20KIT oncogene (C-KIT)KITNGSTissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.10Detected − KIT mutation detected in exons 9, 11, 13 , 14, 17, 18, Exon 9
Requires an escalated dose of TKI for response Better response to sunitinib than imatinib
Exon 11 Associated with TKI sensitivity Exon 13 Primary (nontherapy associated) – associated with TKI
sensitivity Secondary (acquired during therapy) – associated with
TKI resistance Exon 14 Secondary (acquired during therapy) – associated with
TKI resistance Exon 17 D816V – associated with TKI resistance Primary – associated with TKI sensitivity
Secondary – associated with TKI resistance oExon 18 (rare) Secondary (acquired during therapy) – associated with
TKI resistance
21Platelet Derived growth factor receptor (PDGFRA)PDGFRANGSTissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.10Detected – PDGFRA mutation detected in exons 12, 14, 18
Exon 12 – associated with tyrosine kinase inhibitor (TKI) sensitivity.
Exon 14 – associated with tyrosine kinase inhibitor (TKI) sensitivity.
Exon 18 (D842V and D846V) – associated with tyrosine kinase inhibitor (TKI) resistance.
22BRAF V600E analysis.BRAFSanger sequencing.Tissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.7Oncogenic BRAF mutation detected available data suggest resistance to anti-EGFR therapy. BRAF mutation is associated with a worse prognosis.
23PIK3CA (4 mutations) Analysis.PIK3CASanger sequencing.Tissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.7PIK3CA pathogenic mutation indicates tumor may respond to therapies targeted at genes downstream of PI3K in the AKT/mTOR signaling cascade. PIK3CA Exon 20 mutations may indicate resistance to anti-EGFR therapy in wild type KRAS tumors.
24Microsatellite Instability.MSIPCR and Capillary Electrophoresis.EDTA Blood (3ml whole blood):Refrigerated ,Tissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.71. Evaluation of tumor tissue to identify patients at high risk for having hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome.
2. Evaluation of tumor tissue for clinical decision making purposes given the prognostic implications associated with MSI phenotypes.
25MGMT Methylation AnalysisCpG methylation within the MGMT gene promoterEND POINT PCRTissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.101) Prognostication of newly diagnosed glioblastomas 2) Identifying newly diagnosed glioblastomas that may respond to alkylating chemotherapy (temozolomide) 3) Guiding therapy decision making for newly diagnosed glioblastomas in elderly patients (>60 years).
26EGFRT790MEGFRDigital PCRWhole blood 10ml in Streck tube (Cell-Free DNA BCT Tube)3Detection of EGFR T790M circulating mutation is predictive of resistance to EGFR-targeted early
generation tyrosine kinase inhibitor (TKI) therapy.
EGFR T790M is also predictive of response to EGFR T790M mutant-specific TKI therapy (Osimertinib).
27MLH1 Promoter methylationMLH1Methylation specific PCRTissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.10To determine whether MSI-H tumor is resultant of somatic or germline mutation. If it is germline, this test if followed by mutation analysis of MMR genes (MLH1, MSH2, MSH6, PMS2) from the whole blood of the patient.
28HER2-NEUERBB2Digital PCRTissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.7Monitoring metastatic breast cancer patients undergoing trastuzumab-based therapy and to compare these results with those obtained using cancer antigen (CA).
29FISH for ALK/EML4ALKFISHFFPE tissue block10The EML4/ALK fusion gene is responsible for approximately 3-5 % of non-small-cell lung cancer (NSCLC). The vast majority of cases are adenocarcinomas. Two other fusion partners of ALK have been reported in lung cancer - TFG and KIF5B. Up to 12 other translocation partners have been described in anaplastic large-cell lymphomas (ACLC), renal cancer, esophageal squamous cell, colon, and breast carcinoma. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that was discovered in anaplastic large-cell lymphoma (ALC).
30FISH for C-MYCcMycFISHFFPE tissue block10Amplification of MYC has been described in many types of tumor, including breast, cervical and colon cancers, as well as in squamous cell carcinomas of the head and neck, myeloma, non-Hodgkin's lymphoma, gastric adenocarcinomas and ovarian cancer. MYC is the most frequently amplified oncogene and the elevated expression of its gene product correlates with tumor aggression and poor clinical outcome.
31Hereditary breast and ovarian cancer (HBOC) panel.Panel of BRCA1, BRCA2, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53, ATM, BRIP1, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, EPCAM, NBN, NF1 genes.NGSEDTA Blood (3ml whole blood): Refrigerated20To confirm hereditary breast and ovarian cancer (HBOC) syndrome, Cowden, Li Fraumeni and hereditary diffuse gastic cancer (HDGC), that may lead to breast or ovarian cancer.
32Whole Exome SequencingVariant analysis of exonic regions of human genome and exon intron juction of human genome for known and unknow familial disease.NGSEDTA Blood (3 X 3ml whole blood): Refrigerated120Multiple Sequences are aligned with the human reference sequence (Hg19) to identify variantsand Variants related to patient’s phenotype are confirmed by Sanger sequencing as needed
33MET MET proto-oncogeneMET amplification.NGSTissue Block: Room temperature. Also acceptable: Refrigerated. Ship in cooled container during summer months.10In prognostication and therapeutic decisions for cancers (lung cancer) where MET amplification is detected. In lung cancer, MET gene amplification is associated with acquired resistance to EGFR inhibitors. Multiple ongoing trials using EGFR inhibitors, with show sensitivity to crizotinib. Amplification is also associated with tumor progression and a poor prognosis in other tumors- breast, clear cell ovarian, colorectal, esophageal, gastric, glioma, head and neck, mesenchymal, renal and thyroid.
34IDH1 and IDH2 Mutation Screening by SequencingTargeted Mutations in IDH1 & IDH2Sanger SequencingFFPE Tissue Block7 Days(1) Prognostication of newly diagnosed glioblastomas. (2) IDH1 and IDH2 mutations are associated with favorable outcome in all WHO grade gliomas. (3) SNP rs11554137 is associated with unfavorable prognosis. In AML patients IDh mutations indicate unfavorable prognosis if IDH1/IDH2 mutations appear with NPM1 mutations and in the absence of FLT3-ITD mutations.