www.circulogene.com [email protected] 855-614-7083
ONE TUBE + ONE WEEK = COMPLETE RESULTS (DNA + RNA + MSI)
MICROSATELLITE INSTABILITY (MSI) RNA AND MSI MATCHED TO IMMUNOTHERAPIES TO DETECT MISMATCH REPAIR DEFICIENT (MMR)
“FDA APPROVES FIRST CANCER (≥1% OR ≥50%) TREATMENT FOR ANY SOLID TUMOR WITH A SPECIFIC GENETIC FEATURE” ACCURATE IDENTIFICATION OF TUMOR MUTATIONS HTTPS://WWW.FDA.GOV/NEWSEVENTS/NEWSROOM/ PRESSANNOUNCEMENTS/UCM560167.HTM 50 DNA GENES TESTED FOR APPROX. 3,000 KNOWN CANCER MUTATIONS
!"#$%&#' 0678+09:; /%&,%0' J "/%' N< ,.1' < -*$%&#+&")%' 2(+46OPDQ+-6AD6R -*$%&#+&2)1%0' KG= SAMPLE TYPE: Blood COLLECTION DATE: 06/12/2017 DATE RECEIVED: 06/12/2017 REPORT DATE: 06/21/2017 +(2))"05+.J+0%(2*#(Gene(s) Tested: 50 )2#"#$.&"*+#0%&,$&/ (for detailed Test History, see pg 5) Mutations tested include the following: PERSONALIZED GENE PROFILE INDICATION: No Indication Provided Alteration(s) Detected: 7 PHYSICIAN:KRASClary, CODON Dr 12, 13 OR 61 MUTATION; NRAS CODON 12, 13, ORSAMPLE 61 MUTATION; ID: 3558t BRAF V600 MUTATION; Gene(s) Tested: 50 FDA-Approved 1 Alteration(s)Targeted Therapies: Detected: 7 EGFR EXON 18, G719X MUTATION; EGFR EXON 19 DELETION/INSERTION; EGFR EXON 20 INSERTION; SUMMARY OF RESULTS The following 50 genes were tested: FDA-Approved ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, Additional Therapies: 1 ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, SAMPLE TYPE:EGFR EXONCOLLECTION 20, T790M DATE: MUTATION; EGFRDATE EXON RECEIVED: 21, L858R MUTATION; REPORT EGFR DATE: EXON 21, L861Q MUTATION. Targeted Therapies: 1 HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, Blood 06/12/2017 06/12/2017 06/21/2017 Gene(s)see pg Tested: 4 50 NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53, VHL AdditionalOpenAlteration(s) Clinical Therapies: Detected:Trials: 391 3 see pg 410 ZEd ^dZ ^h>d^ )'$*8,'$1&( FDA-Approved PATIENT:INDICATION:Example1T, Example1T GENDER: U AGE: 0 DOB: 06/12/2017 Open Clinical Trials: 390 PERSONALIZED><' E &h^/KE EŽƚĚĞƚĞĐƚĞĚ GENEƌŝnjŽƚŝŶŝď͕ĞƌŝƚŝŶŝď͕ƌŝŐĂƚŝŶŝďŶŽƚŝŶĚŝĐĂƚĞĚ PROFILE No Indication Provided Targetedsee pg 10Therapies: These mutations, relevant in Lung Cancer, The following 50 genes were tested: ZK^ϭ' E &h^/KEABL1, AKT1, ALK, APC,EŽƚĚĞƚĞĐƚĞĚ ATM, BRAF, CDH1, CDKN2A,ƌŝnjŽƚŝŶŝďŶŽƚŝŶĚŝĐĂƚĞĚ CSF1R, CTNNB1, EGFR, ERBB2, wereAdditional tested for andTherapies: determined to be absent: RNA TESTED IN ADDITION TO DNA EGFR exon 18, G719X mutation (Not Found)0 ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, TheseEGFR exonmutations, 20, T790M relevant mutation in Lung (Not Cancer,Found) WͲ>ϭ yWZ ^^/KEThe following 50 genesWŽƐŝƚŝǀĞ were tested: WĞŵďƌŽůŝnjƵŵĂď͕EŝǀŽůƵŵĂďŝŶĚŝĐĂƚĞĚ NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, CLIENT NAME: CLIENT NUMBER: wereEGFR tested exon 21, for L858R and determined mutation (Not to Found)be absent: ABL1,STK11, AKT1, TP53, ALK, VHL APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, House Account 1009 EGFR exon 18,21, G719XL861Q mutation (Not Found) ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, EGFR exon 20,19 deletion/insertionT790M mutation (Not (Not Found) Found) EGFR exon 20 insertion (Not Found) NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, EGFR exon 21, L858R mutation (Not Found) STK11, TP53, VHL EGFR exon 21, L861Q mutation (Not Found) ALTERATIONSEGFR exon 19 deletion/insertion DETECTED (Not Found) PHYSICIAN: Clary, Dr SAMPLE ID: 3558t EGFR/DDhEKd, ZWzd ^dZ ^h>d^ exon 20 insertion (Not Found) )'$*8,'$1&( ZEd ^dZ ^h>d^ )'$*8,'$1&( WͲ>ϭ yWZ ^^/KE WŽƐŝƚŝǀĞ WĞŵďƌŽůŝnjƵŵĂď͕EŝǀŽůƵŵĂďŝŶĚŝĐĂƚĞĚ ><' E &h^/KE EŽƚĚĞƚĞĐƚĞĚ ƌŝnjŽƚŝŶŝď͕ĞƌŝƚŝŶŝď͕ƌŝŐĂƚŝŶŝďŶŽƚŝŶĚŝĐĂƚĞĚ SUMMARYMUTANT FDA TARGETED OFTHERAPIES RESULTSFDA TARGETED THERAPIES CLINICAL TRIALS The following 50 genes were tested: /DDhEKd, ZWzd ^dZ ^h>d^D^/Ͳ, ĞƚĞĐƚĞĚ WĞŵďƌŽůŝnjƵŵĂď͕EŝǀŽůƵŵĂďŝŶĚŝĐĂƚĞĚ)'$*8,'$1&( ZK^ϭ' E &h^/KE EŽƚĚĞƚĞĐƚĞĚ ƌŝnjŽƚŝŶŝď͕ŶŽƚŝŶĚŝĐĂƚĞĚ)'$*8,'$1&( GENE ALTERATION FRACTION (no indicationZEd ^dZ ^h>d^ provided) (for other indications) (DETAILS BELOW) WͲ>ϭ yWZ ^^/KE WŽƐŝƚŝǀĞ WĞŵďƌŽůŝnjƵŵĂď͕EŝǀŽůƵŵĂďŝŶĚŝĐĂƚĞĚ ><' E &h^/KE EŽƚĚĞƚĞĐƚĞĚ ƌŝnjŽƚŝŶŝď͕ĞƌŝƚŝŶŝď͕ƌŝŐĂƚŝŶŝďŶŽƚŝŶĚŝĐĂƚĞĚ SAMPLE TYPE:ABL1,Blood AKT1,COLLECTION ALK, APC, DATE: ATM,06/12/2017 BRAF, CDH1,DATE CDKN2A, RECEIVED: 06/12/2017CSF1R, CTNNB1, REPORT EGFR, DATE: ERBB2,06/21/2017 D^/Ͳ, WĞŵďƌŽůŝnjƵŵĂď͕EŝǀŽůƵŵĂďŝŶĚŝĐĂƚĞĚ None None "*#%0"#$.&(+,%#%-#%,KDR ĞƚĞĐƚĞĚp.Q472H; c.1416A>T 49.4% ZK^ϭ' E &h^/KE EŽƚĚĞƚĞĐƚĞĚ ƌŝnjŽƚŝŶŝď͕ŶŽƚŝŶĚŝĐĂƚĞĚ ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, KDR DESCRIPTION Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, insert domain receptor, is a type III receptor tyrosine kinase. It functions23)'#) as the main4-'()'*!")"-()5"*'6&"+ mediator of VEGF-induced endothelial proliferation,4-'()'*!")"-()5"*'6&"+ survival, migration, tubular morphogenesis$%&#&$'%()*&'%+ "*#%0"#$.&(+,%#%-#%,and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell !"#" '%)"*')&/# 4*'$)&/#Gene(s),789:(;<9;=>1 Tested:,?@>(@AB=>(C9DC; KRASKDR p.Q472H;p.G12D; c.1416A>T c.35G>A 49.4%13.6% NoneNone NoneColon (Codon 13): Cetuximab & Panitumumab KDR DESCRIPTION Contraindicated Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase KRASinsert domainDESCRIPTION receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis Thisand gene,sprouting. a Kirsten The signalling ras oncogene and trafficking homolog of from this thereceptor mammalian are regulated ras gene by multiple family, encodesfactors, including a protein Rab that GTPase, is a member P2Y purine of the nucleotidesmall GTPase receptor, superfamily. integrin alphaVbeta3, A single amino T-cell acid substitutionprotein tyrosine is responsible phosphatase, for anetc.. activating Mutations mutation. of this gene The are transforming implicated inprotein infantile that capillary results hemangiomas. is implicated in [provided various malignancies,by RefSeq, May including 2009] lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008] KRAS p.G12D; c.35G>A 13.6% None Colon (Codon 13): Cetuximab & Panitumumab TP53 p.P72R; c.215C>G 94.6% None ContraindicatedNone DESCRIPTION MOLECULARKRASDESCRIPTION DIAGNOSTICS FOR PRECISION MEDICINE TP53This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid Thissubstitution gene encodes is responsible a tumor for suppressor an activating protein mutation. containing The transforming transcriptional protein activation, that results DNA is implicatedbinding, and in variousoligomerization malignancies, domains. including The lungencoded adenocarcinoma, protein responds mucinous to diverse adenoma, cellular stressesductal carcinoma to regulate of theexpression pancreas of and target colorectal genes, carcinoma. thereby inducing Alternative cell splicingcycle arrest, leads apoptosis,to variants senescence,encoding two DNAisoforms repair, that or differ changes in the inC-terminal metabolism. region. Mutations [provided in by this RefSeq, gene are Jul associated2008] with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016] TP53 p.P72R; c.215C>G 94.6% None None BRAF No Reported Mutation None Melanoma (BRAF Wild Type): TP53 DESCRIPTION This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. TheNivolumab encoded protein & Pembrolizumab responds to diverse cellularIndicated; stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changesDabrafenib, in metabolism. Trametinib, Mutations in this Vemurafenib gene are & associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation Cobimetinibinitiation codons fromNOT identical indicated transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016] No Reported Mutation None Colon (NRAS Wild Type): NRASBRAF No Reported Mutation None Melanoma (BRAF Wild Type): NivolumabCetuximab & Pembrolizumab & Panitumumab Indicated; Dabrafenib, Trametinib, Vemurafenib & Cobimetinib NOT indicated NRAS No Reported Mutation None Colon (NRAS Wild Type): Cetuximab & Panitumumab Lab Director: Dr. Kathryn Clary Client Services: 205-278-1601 Fax: 205-278-1651 3125 Independence Drive, Suite 301, Birmingham, AL 35209 [email protected] C3C46ACE-33E1-9241-A0F4-D69A2C319D02 1 Lab Director: Dr. Kathryn Clary Client Services: 205-278-1601 Fax: 205-278-1651 3125 Independence Drive, Suite 301, Birmingham, AL 35209 [email protected] C3C46ACE-33E1-9241-A0F4-D69A2C319D02 1 www.circulogene.com [email protected] 855-614-7083 DNA TEST MENU GENES FDA-APPROVED TUMOR PROFILES: TESTED: TARGETED THERAPIES: CIRCULO COLORECTAL BRAF, NRAS, PIK3CA, KRAS, MSI CETUXIMAB, PANITUMUMAB, NIVOLUMAB, PEMBROLIZUMAB CIRCULO GASTRIC APC, KRAS, BRAF, PIK3CA, MSI PEMBROLIZUMAB CIRCULO PROSTATE TP53, PTEN, KRAS, PIK3CA, MSI PEMBROLIZUMAB CIRCULO GIST KIT, PDGFRA, BRAF, ERBB2, MSI IMATINIB, PEMBROLIZUMAB CIRCULO HEMOTOLOGICAL FLT3, NPM1, JAK2, ABL1 PONATINIB, RUXOLITINIB,BOSUTINIB, BUSULFAN, DASATINIB, IMATINIB,NILOTINIB, OMACETAXINE CIRCULO BREAST PIK3CA, ERBB2, AKT1, PTEN, MSI ADO-TRASTUZUMAB EMTANSINE, EVEROLIMUS, LAPATINIB, PERTUZUMAB, TRASTUZUMAB, PEMBROLIZUMAB CIRCULO OVARIAN KRAS, BRAF, PIK3CA, PTEN, MSI PEMBROLIZUMAB CIRCULO MELANOMA BRAF, NRAS, KIT, MSI DABRAFENIB, TRAMETINIB, VEMURAFENIB, COBIMETINIB, IMATINIB, PEMBROLIZUMAB CIRCULO PANCREATIC KRAS, CDKN2A, TP53, MSI ERLOTINIB, PEMBROLIZUMAB CIRCULO BLADDER TP53, PTEN, RB1, PIK3CA, MSI PEMBROLIZUMAB COMPREHENSIVE LUNG EGFR, KRAS, ALK, PIK3CA, BRAF, AFATINIB, ERLOTINIB, GEFITINIB, CERITINIB, MSI, ALK GENE FUSION (RNA) CRIZOTINIB, DABRAFENIB, TRAMETINIB, VEMURAFENIB, ROS1 GENE FUSION (RNA) ALECTINIB, BRIGATINIB, PEMBROLIZUMAB, NIVOLUMAB PD-L1 EXPRESSION (RNA) RNA TESTING ALK GENE FUSION (RNA) ALECTINIB, BRIGATINIB, CRIZOTINIB, CERITINIB, ROS1 GENE FUSION (RNA) PEMBROLIZUMAB TESTS MATCHING TO PD-L1 EXPRESSION PEMBROLIZUMAB, NIVOLUMAB IMMUNOTHERAPY FDA-Approved Targeted Therapies Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules that are involved in the growth, progression and spread of cancer. Each personalized gene profile provides information on current FDA-approved treatment options proven effective for the tumor DNA and RNA mutations identified. Sources: cancer.gov and fda.gov www.circulogene.com [email protected] 855-614-7083